Publications by authors named "Michiaki Myotoku"

35 Publications

Visualization of cross-resistance between antimicrobial agents by asymmetric multidimensional scaling.

J Clin Pharm Ther 2021 Nov 24. Epub 2021 Nov 24.

Faculty of Management and Information Sciences, Tama University, Tokyo, Japan.

What Is Known And Objective: In our previous studies, we developed a cross-resistance rate (CRR) correlation diagram (CRR diagram) that visually captures the magnitude of CRRs between antimicrobials using scatter plots. We used asymmetric multidimensional scaling (MDS) to transform cross-resistance similarities between antimicrobials into a 2-dimensional map and attempted to visually express them. We also explored the antibiograms of Pseudomonas aeruginosa before and after the transfer to newly built hospitals, and we determined by the CRR diagram that the CRRs among β-lactam antimicrobials other than carbapenems decreased substantially with the facility transfer. The present study tests whether the analysis of CRRs by asymmetric MDS can be used as new visual information that is easy for healthcare professionals to understand.

Method: We tested the impact of changes in the nosocomial environment due to institutional transfers on CRRs among antimicrobials in asymmetric MDS, as well as contrasted the asymmetric MDS map and CRR diagram.

Results And Discussion: In the asymmetric MDS map, antimicrobial groups with the same mechanism of action were displayed close together, and antimicrobial groups with different mechanisms of action were displayed separately. The asymmetric MDS map drawn solely for antimicrobials belonging to the group with the same mechanism of action showed similarities to the CRR diagram. Also, the distance of each antimicrobial to other antimicrobials shown in the asymmetric MDS map was negatively correlated with the CRRs for them against that antimicrobial.

What Is New And Conclusion: The asymmetric MDS map expresses the dissimilarity as distances between agents, and there are no meanings or units on the ordinate and abscissa axes of the output map. In contrast, the CRR diagram expresses the antimicrobials' resistance status as values, such as resistance rate and CRR. By analysing the CRRs in the asymmetric MDS, it is feasible to visually recognize cross-resistance similarities between antimicrobial groups as distances. The use of the asymmetric MDS combined with the CRR diagram allows us to visually understand the resistance and cross-resistance status of each antimicrobial agent as a 2-dimensional map, as well as to understand the trends and characteristics of the data by means of quantitative values.
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http://dx.doi.org/10.1111/jcpt.13564DOI Listing
November 2021

Bacterial contamination of lightproof covers for high-calorie infusion solutions in wards.

Int J Med Sci 2021 23;18(16):3708-3711. Epub 2021 Sep 23.

Faculty of Pharmacy, Osaka Ohtani University.

Deterioration of drugs due to light exposure is one of the major concerns, especially regarding protection of high-calorie infusion solutions, lightproof covers are used in hospitals. In the absence of any set standards regarding their usage, they are often reused. This study aimed to investigate bacterial contamination of lightproof covers used in hospital wards. For this, lightproof covers which had been used or stored in wards were collected and bacterial cultures were carried out from them. Examination of the cultures revealed that bacteria were present in the used lightproof covers. The bacterial species detected in the used lightproof covers were species Coagulase-negative (CNS) and Methicillin-resistant (MRSA). species and CNS were also detected in lightproof covers stored in wards, whereas MRSA was not detected. Intestinal bacteria were detected in only one lightproof cover. However, no bacteria were detected from either inside or outside of the unused lightproof covers that were stored in the drugs department. After allowing the unused lightproof covers stored in the drugs department to stand for 24 h, species and CNS were detected in only one of the covers, whereas no bacteria was detected in other covers. These results indicate that there is a risk of bacterial contamination in the reuse of lightproof covers and that they should either be disposed off properly after usage or hand, finger disinfectants should be used while handling them to prevent any possible contamination.
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http://dx.doi.org/10.7150/ijms.62193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579297PMC
September 2021

Effects of concurrent and staggered dosing of semi-solid enteral nutrients on pharmacokinetic behavior of antiepileptic drugs after oral administration in rats.

PLoS One 2021 9;16(11):e0259400. Epub 2021 Nov 9.

Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka, Japan.

Background: The use of enteral nutrients plays a highly important role in accurate nutrition management, but limited information is currently available on the cautionary points of semi-solid enteral nutrients.

Aim: In this study, we examined whether the pharmacokinetic profiles of sodium valproate (SVA), levetiracetam (LEV), and carbamazepine (CBZ) are affected by altering the dosing time of RACOL®-NF Semi Solid for Enteral Use (RASS), a prescribed semi-solid formula. We also investigated whether the pharmacokinetic interaction observed in this study can be avoided by staggered dosing of the chemical drug and semi-solid enteral nutrient.

Methods: The plasma concentration of SVA, LEV and CBZ after oral administration was measured by LC-MS/MS method.

Results: There was no difference in pharmacokinetic characteristics of SVA and LEV when the dosing time of RASS was altered. On the other hand, the plasma concentration of CBZ after oral administration at all sampling points decreased with the extension of the dosing time of RASS, which was consistent with the Cmax and AUC. However, no significant difference was observed in the pharmacokinetic profiles or parameters of CBZ between the short-term and long-term RASS dosing groups by prolonging the administered interval of CBZ and RASS for 2 hr.

Conclusion: We concluded that the pharmacokinetic profiles of CBZ, but not SVA and LEV, after its oral administration are affected by the dosing time of RASS, but staggered administration of CBZ and RASS prevented their interaction.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0259400PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577762PMC
November 2021

Microbial growth and importance of flushing inside closed-type infusion devices during administration of lipid emulsion setting.

Int J Med Sci 2021 26;18(14):3106-3111. Epub 2021 Jun 26.

Faculty of Pharmacy, Osaka Ohtani University.

We investigated the extent of growth of microorganisms with simultaneous administration of lipid emulsions with infusions for Total Parenteral Nutrition (TPN), assuming that the lipid emulsions contaminated with microorganisms are stagnant in a closed-type infusion device. We also investigated if bacterial growth can be prevented in the infusion device by flushing the inside of the infusion device with saline solution after the administration of lipid emulsion from the side tube setting. We made a preparation by adding to the lipid emulsion and started the infusion simultaneously with the infusion solution for TPN and lipid emulsion with the piggyback method. Immediately after the completion of lipid emulsion infusion, we conducted flushing with saline solution. The volume of saline solution was none, 5, 10, or 20 mL at a flow rate of 1 mL/s. Infusion solution that was stagnant in the infusion device was collected immediately before completing the lipid emulsion infusion and 20 h after flushing, i.e., 24 h after starting the infusion for TPN, and the number of viable bacteria was determined. The number of viable increased in the infusion device of all three species used in this experiment 24 h after starting the lipid emulsion infusion without flushing. We found that bacterial growth could be prevented through flushing with saline solution after the completion of lipid emulsion infusion and flushing out the stagnant infusion solution in the closed-type infusion device. We found that if was present in the closed-type infusion device, it would multiply. We also found that the number of viable bacteria varied according to the variety and internal structure of the closed-type infusion device as well as the liquid volume used for flushing, although flushing can prevent the growth of microorganisms. Proper management and manipulation of infusion is required to prevent infection.
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http://dx.doi.org/10.7150/ijms.60200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364470PMC
June 2021

Monitoring antimicrobial cross-resistance with cross-resistance rate correlation diagrams: Changes in antibiotic susceptibility of Pseudomonas aeruginosa due to hospital relocation.

J Clin Pharm Ther 2021 Apr 28;46(2):395-407. Epub 2020 Oct 28.

Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi-shi, Osaka, Japan.

What Is Known And Objective: Though most medical institutions calculate antimicrobial susceptibility and resistance rates of microbes isolated at their own facility as part of their efforts to promote the proper use of antibiotics, very few, if any, regularly monitor cross-resistance rates between antimicrobial agents. The authors have devised a tool in the form of a cross-resistance rate correlation diagram (CRR diagram) that allows easy identification of increases or decreases in, or changes in the pattern of, antimicrobial cross-resistance. The objective was to perform an analysis by CRR diagrams of the effect of relocation to a newly built facility on antimicrobial resistance and cross-resistance rates at a medical facility.

Methods: The Sakai City Medical Center relocated in July 2015 to a newly built facility located in a different primary medical care zone 3.5 km away. Based on the drug susceptibility test data compiled at the Sakai City Medical Center, resistance and cross-resistance rates of Pseudomonas aeruginosa before and after the relocation of the hospital facility were calculated, and the rates were assessed using CRR diagrams.

Results And Discussion: It was possible to confirm the effect of hospital relocation on antibiotic susceptibility of P aeruginosa in terms of changes in resistance and cross-resistance rates. The effect of the facility's relocation on cross-resistance rates was particularly notable with respect to β-lactam antibiotics: cross-resistance rates among β-lactams decreased substantially, represented as a large wedge-shaped change towards the origin on the CRR diagram. Rates of cross-resistance between classes of antibiotics with a different mechanism of antibiotic action changed little.

What Is New And Conclusion: Including cross-resistance rates in the routine monitoring of resistance and susceptibility rates practiced by a medical institution can provide a comprehensive insight into the dynamics of bacterial flora in the facility. CRR diagrams, which allow visualization of the status and changes in cross-resistance, not only provide a new perspective for clinicians, but they also contribute to the proper use of antibiotics and serve as a tool in the education of healthcare professionals and students about antibiotic resistance.
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http://dx.doi.org/10.1111/jcpt.13296DOI Listing
April 2021

Influence of analysis conditions for antimicrobial susceptibility test data on susceptibility rates.

PLoS One 2020 23;15(6):e0235059. Epub 2020 Jun 23.

Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi-shi, Osaka, Japan.

Background: To support effective antibiotic selection in empirical treatments, infection control interventions, and antimicrobial resistance containment strategies, many medical institutions collect antimicrobial susceptibility test data conducted at their facilities to prepare cumulative antibiograms.

Aim: To evaluate how the setpoints of duplicate isolate removal period and data collection period affect the calculated susceptibility rates in antibiograms.

Methods: The Sakai City Medical Center is a regional core hospital for tertiary emergency medical care with 480 beds for general clinical care. In this study, all the Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae isolates collected at the Sakai City Medical Center Clinical Laboratory between July 2013 and December 2018 were subjected to antimicrobial susceptibility tests and the resulting data was analyzed.

Findings: The longer the duplicate isolate removal period, the fewer the isolates are available for every bacterial species. Differences in the length of the duplicate isolate removal period affected P. aeruginosa susceptibility rates to β-lactam antibiotics by up to 10.8%. The setpoint of the data collection period affected the antimicrobial susceptibility rates by up to 7.3%. We found that a significant change in susceptibility could be missed depending on the setting of the data collection period, in preparing antibiogram of β-lactam antibiotics for P. aeruginosa.

Conclusions: When referring to antibiograms, medical professionals involved in infectious disease treatment should be aware that the parameter values, such as the duplicate isolate removal period and the data collection period, affect P. aeruginosa susceptibility rates especially to β-lactam antibiotics. And antibiogram should be updated within the shortest time period that is practically possible, taking into account restrictions such as numbers of specimen.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235059PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310835PMC
September 2020

Drug-induced lung disease adverse effect with Ledipasvir Acetonate/Sofosbuvir.

J Pharm Health Care Sci 2020 2;6. Epub 2020 Apr 2.

1Laboratory of Practical Pharmacy and Pharmaceutical Care, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1, Nishikiori-kita, Tondabayashi, Osaka, 584-8540 Japan.

Background: Interferon and ribavirin have been used as therapeutic agents for chronic hepatitis C infection or C-compensated cirrhosis in the conventional treatment. Hepatitis C virus (HCV) -specific direct-acting antiviral agents that directly inhibit the growth process of HCV have been approved since 2011. However, in the early post-marketing vigilance phase of ledipasvir acetonate/sofosbuvir (LDV/SOF), there were reports of interstitial lung disease in 4 out of 32,700 cases with death in 1 case; the onset mechanism is unknown.

Case Presentation: Treatment for hepatitis C was deemed to be necessary, and the patient was referred to our hospital. Oral administration of LDV/SOF was started. On day 8 of administration, a fever of 38-39 °C and coughing were observed followed by the gradual appearance of shortness of breath. As there was no improvement, the patient visited her primary care physician on day 16 of administration and the patient was brought urgently to our hospital on the same day. Blood tests and imaging tests were conducted at our hospital on the day of emergency transport; inflammatory response markers showed abnormal values, and sialylated carbohydrate antigen Krebs von den Lungen-6 was within the normal value range at 303 U/mL. Because the possibility of infection was low based on results of imaging and bronchoalveolar lavage, drug-induced lung disease was suspected, LDV/SOF administration was discontinued, and steroid administration was started. Following steroid pulse therapy, treatment with oral prednisolone tablets was gradually tapered. The patient's symptoms were relieved and she was discharged.

Conclusions: The patient's medication history in this case indicated that there were no drugs taken before or after administration of LDV/SOF until the adverse reaction occurred, and there were no supplements or dietary supplements taken. Therefore, LDV/SOF has been proposed as the cause of the suspected adverse effect. Pharmacists should try to collect adverse effect reports to identify adverse effects early.
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http://dx.doi.org/10.1186/s40780-020-00162-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114806PMC
April 2020

Effects of semi-solidification of enteral nutrients on the pharmacokinetic behavior of orally administered carbamazepine in rats.

Int J Med Sci 2019 7;16(9):1283-1286. Epub 2019 Sep 7.

Laboratory of Practical Pharmacy and Pharmaceutical Care, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, 584-0066, Japan.

The use of semi-solid enteral nutrients plays an extremely important role in accurate nutrition management. In the present study, we compared the pharmacokinetic profile of orally administered carbamazepine (CBZ) in rats treated with liquid RACOL, semi-solid RACOL, and HINE E-gel, which are enteral nutrients marketed in Japan. Since liquid and semi-solid formulations are both marketed in Japan for RACOL, liquid RACOL was orally administered to control rats. The serum concentration of CBZ at each sampling point was lower in the semi-solid RACOL-treated group than in the liquid RACOL-treated group. No significant differences were observed in the pharmacokinetic behavior of CBZ between the semi-solid RACOL-treated and HINE E-gel-treated groups. Regarding pharmacokinetic parameters, the impact of the area under the curve (AUC) was the liquid RACOL group > the semi-solid RACOL group ≈ the HINE E-gel group. Therefore, we concluded that serum concentrations of CBZ were lower when concurrently treating with semi-solid enteral nutrients than when simultaneously processing liquid enteral nutrients.
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http://dx.doi.org/10.7150/ijms.35471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775268PMC
April 2020

Enhanced anti-cancer activity by menthol in HepG2 cells exposed to paclitaxel and vincristine: possible involvement of CYP3A4 downregulation.

Drug Metab Pers Ther 2019 03 6;34(1). Epub 2019 Mar 6.

Laboratory of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Japan.

Background Menthol is widely used as a constituent of functional foods and chemical drugs. In the present study, we investigated changes in the expression of cytochrome P450 isoform CYP3A4mRNA after treating human hepatocellular carcinoma HepG2 cells with menthol. We also examined the effects of pretreatment with menthol on the cytotoxic activity of paclitaxel (PAC) and vincristine (VIN), which are substrates of CYP3A4, in the cells. Methods HepG2 cells were maintained in Dulbecco's Modified Eagle's Medium. Expression of CYP3A4 was examined by the real-time polymerase chain reaction. Survival rate of HepG2 cells was evaluated by the MTT assay. Results The gene expression level of CYP3A4 in HepG2 cells was significantly reduced by treatment with menthol for 1 day. The viability of HepG2 cells was not affected by treatment with menthol alone once a day for two consecutive days. The degree of reduction in cell viability by PAC or VIN in HepG2 cells was significantly increased by menthol treatment for 24 h prior to exposure to these anti-cancer drugs. Conclusions These results demonstrate that menthol enhanced the anti-tumor effects of PAC and VIN through the downregulation of CYP3A4 in HepG2 cells without exerting cytotoxic activity.
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http://dx.doi.org/10.1515/dmpt-2018-0029DOI Listing
March 2019

Compatibility of Intravenous Fat Emulsion with Antibiotics for Secondary Piggyback Infusion.

Ann Nutr Metab 2018 13;73(3):227-233. Epub 2018 Sep 13.

Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan.

Background: The Guidelines for Parenteral and Enteral Nutrition in Japan state that parenteral fat emulsion can be infused through a secondary administration set. We tested the compatibility of fat emulsion with antibiotics in piggyback infusions in terms of changes in the size distribution of fat particles.

Methods: Test mixtures of 5% glucose solution, fat emulsion, and 25 antibiotic agents were prepared in the ratio appropriate for piggyback infusion (33: 10: 40) and analyzed serially for the number of fine particles by size using a light-shielded automatic fine particle counter.

Results: No marked changes were observed in the 12 β-lactam antibacterial drugs, clindamycin phosphate, teicoplanin, trimethoprim/sulfamethoxazole, and micafungin sodium even at 24 h after preparation. The particle size in the mixture containing vancomycin hydrochloride, levofloxacin hydrate, metronidazole, and fluconazole gradually increased after preparation. The particle size in the mixture containing gentamicin sulfate, arbekacin sulfate, minocycline hydrochloride, ciprofloxacin, and fosfomycin sodium changed significantly after preparation.

Conclusions: The changes in the particle size observed with some drugs suggest that they may cause changes in the lipid particle size during administration and, therefore, those antibiotics agents should not be administered concurrently with fat emulsion.
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http://dx.doi.org/10.1159/000492940DOI Listing
November 2019

Alterations in Pharmacokinetics of Orally Administered Carbamazepine in Rats Treated with Sodium alginate: Possible Interaction between Therapeutic Drugs and Semi-solid Enteral Nutrients.

Drug Res (Stuttg) 2019 Feb 13;69(3):168-172. Epub 2018 Aug 13.

Faculty of Pharmacy, Laboratory of Practical Pharmacy and Pharmaceutical Care, Osaka Ohtani University, Tondabayashi, Japan.

Objective: The use of enteral nutrients plays an extremely important role in accurate nutrition management. Sodium alginate (SA) is frequently used for the semi-solidification of enteral nutrients. In the present study, we investigated whether the pharmacokinetic profile of orally administered carbamazepine (CBZ) is altered by a treatment with SA immediately before and after dosing of the drug. Furthermore, the adsorption effects of SA on CBZ were examined using an in vitro analysis.

Method: SA was orally administered to rats just before and immediately after CBZ dosing. The CBZ concentration profile following its oral administration was analyzed by a non-compartmental method. The adsorption of CBZ onto SA was evaluated after centrifugation using an ultrafiltration device.

Findings: The serum concentration of orally administered CBZ at each sampling point was reduced by the treatment with SA, and the extent of the decrease observed in the concentration of CBZ was larger when SA was ingested immediately after administration of the drug, which was consistent with the alteration observed in the value of the area under the curve (AUC). No significant differences were noted in the elimination rate at the terminal phase (k) among the groups. In the in vitro assay, CBZ was adsorbed by SA in the solution used to reflect fluid in the intestinal tract.

Conclusions: The pharmacological efficacies of CBZ might be reduced by SA through the pharmacokinetic interactions, and that the careful attention should be paid to the timing of administration of CBZ and semi-solid enteral nutrients.
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http://dx.doi.org/10.1055/a-0662-5701DOI Listing
February 2019

Prevention of Doxorubicin-Induced Renal Toxicity by Theanine in Rats.

Pharmacology 2018 25;101(3-4):219-224. Epub 2018 Jan 25.

Laboratory of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Japan.

Doxorubicin (DOX) is a highly potent anti-neoplastic agent widely used in clinical practice, but its dosage and duration of administration are strictly limited due to dose-related organ damage. In the present study, we examined whether theanine, an amino acid derivative found in green tea leaves, can protect against DOX-induced acute nephrotoxicity in rats. Decreases in the creatinine clearance by DOX administration were attenuated by concurrent treatment with theanine, which was consistent with the change in histological renal images assessed by microscopic examination. Theanine had no effect on the distribution of DOX to the kidney. The production of lipid peroxide in the kidney after DOX administration was suppressed by concurrent treatment with theanine. Reduced glutathione content, but not superoxide dismutase activity, was decreased following DOX administration, whereas this change was suppressed when theanine was given in combination with DOX. These results suggest that theanine prevents DOX-induced acute nephrotoxicity through its antioxidant properties.
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http://dx.doi.org/10.1159/000486625DOI Listing
August 2018

Bactericidal effects of deep ultraviolet light-emitting diode for solutions during intravenous infusion.

Int J Med Sci 2018 1;15(2):101-107. Epub 2018 Jan 1.

Faculty of Pharmacy, Osaka Ohtani University.

Ultraviolet irradiation is effectively used as a disinfection method for inactivating microorganisms. We investigated the bactericidal effects by irradiation with a deep-ultraviolet light-emitting diode (DUV-LED) on the causative microorganisms of catheter related blood stream infection contaminating the solution for intravenous infusion. For irradiation, prototype modules for water disinfection with a DUV-LED were used. Experiments were conducted on five kinds of microorganisms. We examined the dependence of bactericidal action on eleven solutions. Administration sets were carried out three types. When the administration set JY-PB343L containing the infusion tube made of polybutadiene was used, the bactericidal action of the DUV-LED against all tested microorganisms in the physiological saline solutions was considered to be effective. We confirmed that the number of viable bacteria decreased in 5% glucose solution and electrolyte infusions with DUV-LED irradiation. These results indicate that the DUV-LED irradiation has bactericidal effects in glucose infusion and electrolyte infusions by irradiating via a plasticizer-free polybutadiene administration set. We consider DUV-LED irradiation to be clinically applicable.
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http://dx.doi.org/10.7150/ijms.22206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765722PMC
August 2018

In vitro and in vivo effects of selected fibers on the pharmacokinetics of orally administered carbamazepine: Possible interaction between therapeutic drugs and semisolid enteral nutrients.

Nutrition 2018 02 10;46:44-47. Epub 2017 Aug 10.

Laboratory of Practical Pharmacy and Pharmaceutical Care, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Japan. Electronic address:

Objective: The management of nutrition using semisolid enteral nutrients is considered useful for avoiding the adverse effects associated with liquid enteral nutrients. In the present study, we used an in vitro analysis to investigate whether carbamazepine (CBZ) is adsorbed by the fibers included in semisolid enteral nutrients. The effects of these fibers on the pharmacokinetic profile of CBZ following its oral administration were also examined in rats.

Methods: The adsorption of CBZ onto fibers was examined by absorbance monitoring of the filtrate after centrifugation using an ultrafiltration device. Viscosities of each solution were measured by rotational viscosimeter. The CBZ concentration profile after its oral administration (50 mg/kg) was analyzed by a noncompartmental method.

Results: In the two solutions used to reflect gastric juice and fluid in the intestinal tract, CBZ was more strongly adsorbed by water-soluble fibers (guar gum and xanthan gum) than by insoluble fibers (dextrin hydrate). The adsorption of CBZ also was observed even if the concentrations of guar gum and xanthan gum were reduced to such an extent that viscosity was 0 Pa・s. The pharmacokinetic examination of orally administered CBZ revealed that the area under the curve was significantly lower in the guar gum and xanthan gum groups than in the control group.

Conclusion: CBZ was adsorbed by fibers used for the semisolidification of enteral nutrients, which may be partially responsible for the alterations observed in the pharmacokinetic profile of CBZ.
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http://dx.doi.org/10.1016/j.nut.2017.08.006DOI Listing
February 2018

Water Soluble Vitamins Enhance the Growth of Microorganisms in Peripheral Parenteral Nutrition Solutions.

Int J Med Sci 2017 19;14(12):1213-1219. Epub 2017 Sep 19.

Laboratory of Practical Pharmacy and Pharmaceutical Care, Faculty of Pharmacy, Osaka Ohtani University.

Peripheral parenteral nutrition (PPN) solutions contain amino acids, glucose, and electrolytes, with or without some water soluble vitamins. Peripheral venous catheters are one of the causes of catheter related blood stream infection (CRBSI), which requires infection control. In Japan, PPN solutions have rarely been prepared under aseptic conditions. However, in recent years, the necessity of adding vitamins to infusions has been reported. Therefore, we investigated the effects of water soluble vitamins on growth of microorganisms in PPN solutions. AMINOFLUID (AF), BFLUID (BF), PARESAFE (PS) and PAREPLUS (PP) PPN solutions were used. Water soluble vitamins contained in PP were also used. Causative microorganisms of CRBSI were used. decreased after 24 hours or 48 hours in all solutions. On the other hand, , , and increased, especially in PP. When each water soluble vitamin was added to BF and PS, growth of was greater in solutions that contained nicotinamide than in solutions that contained other vitamins. As for , they grew in all test solutions. grew especially well in solutions that contained biotin. When commercial amino acids and glucose solutions with electrolytes are administered, in particular those containing multivitamins or water soluble vitamins, efforts to control infection must be taken to prevent proliferation of microorganisms.
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http://dx.doi.org/10.7150/ijms.21424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666554PMC
June 2018

Altered tolbutamide pharmacokinetics by a decrease in hepatic expression of CYP2C6/11 in rats pretreated with 5-fluorouracil.

Xenobiotica 2018 Jan 31;48(1):53-59. Epub 2017 Jan 31.

a Laboratory of Clinical Pharmacy and Therapeutics , Faculty of Pharmacy, Osaka Ohtani University , Tondabayashi , Japan and.

1. We investigated the change in the pharmacokinetic profile of tolbutamide (TB), a substrate for CYP2C6/11, 4 days after single administration of 5-fluorouracil (5-FU), and the hepatic gene expression and activity of CYP2C6/11 were also examined in 5-FU-pretreated rats. 2. Regarding the pharmacokinetic parameters of the 5-FU group, the area under the curve (AUC) was significantly increased, and correspondingly, the elimination rate constant at the terminal phase (k) was significantly decreased without significant change in the volume of distribution at the steady state (Vd). 3. The metabolic production of 4-hydroxylated TB in hepatic microsomes was significantly reduced by the administration of 5-FU. 4. The expression level of mRNAs for hepatic CYP2C6 and CYP2C11 was significantly lower than in the control group when the rats were pretreated with 5-FU. 5. These results demonstrated that the pharmacokinetic profile of TB was altered by the treatment with 5-FU through a metabolic process, which may be responsible for the decreased CYP2C6/11 expression at mRNA levels.
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http://dx.doi.org/10.1080/00498254.2017.1278808DOI Listing
January 2018

Importance of Pharmaceutical Training and Clinical Research at Medical Facilities.

Authors:
Michiaki Myotoku

Yakugaku Zasshi 2017 ;137(1):13-16

Laboratory of Practical Pharmacy and Pharmaceutical Care, Faculty of Pharmacy, Osaka Ohtani University.

To respond to advancements in medical techniques, and to address the separation of medical and dispensary practices, clinical professors are required to educate human resource staff to become highly-skilled pharmacists. For this purpose, it is extremely important for these professors to learn about cutting-edge practical skills and knowledge, as well as to advance their expertise. In addition, they need to conduct clinical research in cooperation with relevant facilities. As our university does not have its own hospital or pharmacy, it is important to provide training for clinical professors in clinical facilities. Such training mainly involves medical teams' in-hospital rounds and participation in conferences (nutrition support team; NST), operation of the pharmacy department, and intervention targeting improvement in the department's duties. We have conducted collaborative studies, provided research instructions, implemented studies aimed at improving the department's work (pharmacists appointed on wards at all times to ensure medical safety) as well as studies regarding team medical care (nutritional evaluation during outpatient chemotherapy), and resolved issues regarding this work (drug solution mixability in a hand-held constant infusion pump, and a safe pump-filling methods). Thus, it has become possible to keep track of the current state of a pharmacists' work within team medical care, to access information about novel drugs, to view clinical and prescription-claim data, to cooperate with other professionals (e.g., doctors and nurses), to promote pharmacists' self-awareness of their roles in cooperative medical practice, and to effectively maintain the hospital's clinical settings.
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http://dx.doi.org/10.1248/yakushi.16-00220-3DOI Listing
May 2017

Enhanced Understanding of the Levels of Palliative Care in Pharmacy Students Through Participating in Clinical Training in Hospitals.

J Pharm Pract 2017 Jun 18;30(3):313-317. Epub 2016 Mar 18.

3 Faculty of Pharmacy, Laboratory of Clinical Pharmaceutics, Osaka Ohtani University, Tondabayashi, Osaka, Japan.

Objective: A palliative care knowledge survey was conducted involving pharmacy students to examine their perceived usefulness and the educational effect of clinical training in hospitals.

Methods: A questionnaire sheet was distributed to fifth-year pharmacy students before and after clinical training. The questionnaire consisted of questions to clarify the details of palliative care-related training in hospitals and students' knowledge of such care. The respondents were divided into 2 groups: those who participated in palliative care team (PCT) rounds (group A: 57) and those who did not (group B: 57).

Results: The mean total correct answer rate markedly increased after training in group A, from 37.9 to 47.1% (P < .01). Such an increase was also observed in the domains of philosophy and pain in this group ( P < .01). In contrast, group B did not show differences in the mean correct answer rate between before and after training; there was no significant increase in the rate in any domain.

Conclusion: Pharmacy students' knowledge was enhanced by participating in the PCT, confirming the usefulness of such participation during training as part of palliative care education.
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http://dx.doi.org/10.1177/0897190016637528DOI Listing
June 2017

[The Current State of Inappropriate Drug Use among Elderly Assisted-Living Residents].

Gan To Kagaku Ryoho 2015 Dec;42 Suppl 1:43-4

Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Faculty of Pharmacy, Osaka Ohtani University.

Previous studies have reported that elderly assisted-living residents use multiple drug combinations and inappropriate drugs.The aim of this study was to assess the drug use and its consequences in residents of a nursing facility.We examined the prescriptions of all residents in a nursing facility in Osaka from their medical records.Of the total 67 residents, 48 were women.The average age of the residents was 86 years, the average number of prescription drugs they took was 6.4, and the average number of diseases present was 4.9. Correlation between the number of diseases and the drugs taken was significant (p<0.05), but the correlation between the degree of independence for activities of daily living and the number of the drugs taken was not significant.The most commonly present health condition was bone fracture.About 50% of the residents used a psychotropic drug and prescription drugs such as amantadine and hydroxyzine, which are not advisable for elderly people.It is necessary for the elderly to avoid the use of drugs that cause delirium and drowsiness, and future studies should focus on methods to prevent disuse syndrome in the elderly.
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December 2015

[Changes in Medical Safety Interventions Conducted by Ward-based Pharmacists since the Introduction of Their Services in Complex Medical Ward].

Yakugaku Zasshi 2015 ;135(9):1069-76

Department of Pharmacy, Municipal Ikeda Hospital.

Despite an increase in the number of reports on medical safety interventions conducted by ward-based pharmacists, only a few reports have classified intervention cases in detail. We classified and compared the types of medical safety intervention conducted by ward-based pharmacists since the introduction of their services. The interventions were classified into: cases that were identified by pharmacists or through asking questions about physicians' prescriptions before dispensing medications (active interventions); and those in which pharmacy technicians could contribute to medical safety by receiving inquiries from patients or healthcare providers (passive interventions). The numbers of the two types of intervention were compared. The number of interventions significantly increased after the introduction of ward-based clinical pharmacy services. Especially, the numbers of cases identified during ward rounds conducted by ward-based pharmacists (active interventions) and those identified by receiving inquiries from physicians or nurses (passive interventions) significantly increased, possibly because the collection of patient information was performed more efficiently by conducting ward rounds, and an environment where physicians and nurses can easily make inquiries to pharmacists was established after increasing the time pharmacists spend on hospital wards. The results demonstrate that the introduction of ward-based clinical pharmacy services has improved communication with patients, facilitated information-sharing among physicians, nurses, and other healthcare providers, contributed to the safer management of pharmaceutical operations, and increased interest of patients.
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http://dx.doi.org/10.1248/yakushi.15-00008DOI Listing
August 2016

Effects of eicosapentaenoic acid on hepatic dyslipidemia and oxidative stress in high fat diet-induced steatosis.

Int J Food Sci Nutr 2015 28;66(5):569-73. Epub 2015 May 28.

Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohatani University , Tondabayashi, Osaka , Japan.

We investigated the ability of eicosapentaenoic acid (EPA) to prevent high-fat diet (HFD)-induced obesity and non-alcoholic fatty liver disease (NAFLD). Male C57BL/6J mice were fed standard chow (5.3% fat content), an HFD (32.0% fat content) or an HFD + EPA (1 g/kg/day EPA for the last 6 weeks) for 12 weeks. Serum total cholesterol, hepatic triglyceride and total cholesterol levels were significantly increased in the HFD group, in comparison with those of normal mice (p < 0.01). In contrast, hepatic triglyceride and total cholesterol levels were significantly decreased in the HFD + EPA group, in comparison with those of the HFD group (p < 0.05). In addition, EPA decreased the body weight of obese mice and improved hepatic function. Hepatic superoxide dismutase activity and glutathione levels were significantly decreased in obese mice, but increased with EPA administration. Our data suggest that EPA supplementation has a beneficial effect on NAFLD progression.
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http://dx.doi.org/10.3109/09637486.2015.1042848DOI Listing
May 2016

[Evaluation of the pharmaceutical stability of polaprezinc/sodium alginate gargle solution containing lidocaine].

Gan To Kagaku Ryoho 2015 Feb;42(2):207-10

Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University.

Objective: A gargle solution(L-P/AG)for the treatment of painful stomatitis was prepared by adding lidocaine to a polaprezinc/sodium alginate gargle solution(P/AG), and its pharmaceutical stability was evaluated.

Methods: L-P/AG was stored at 5, 25, and 40°C. The strengths of polaprezinc and lidocaine were determined. The viscosity and pH of L-P/AG were also determined, and its appearance was evaluated.

Results: When stored at 5 or 25°C in a dark place, L-P/AG showed neither reduction in the strength of either drug nor did it show a change in the viscosity, pH, or appearance. When stored exposed to light at 40°C, L-P/AG showed reductions in the strength of both drugs, as well as in viscosity and pH; furthermore, a change in appearance was noted.

Discussion: L-P/AG prepared for the treatment of painful stomatitis remains pharmaceutically stable for 28 days when stored at 25°C in a dark place.
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February 2015

[Thoughts and suggestions of pharmacists who participated in a home medical care training workshop in a local area].

Gan To Kagaku Ryoho 2014 Dec;41 Suppl 1:47-9

Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University.

We organized a home medical care training workshop to offer community pharmacists an opportunity to advance home medical care by allowing pharmacists in regional medicine to collaborate with local pharmacist groups. A questionnaire was administered to all participants after the workshop. On average, participants rated the overall quality of the workshop as 8.46 out of 10. Our results revealed that 72.5% of participating pharmacists were experienced in home medical care, with the majority having between 5 and 10 years of experience. Participants suggested that the qualities necessary for effective home medical care were knowledge of home-based care, positive attitude, and coordination with different home medical care staff members. Participants also made suggestions for lectures in future workshops (e.g., upskilling to improve home medical care expertise). In conclusion, participants in a home medical care training workshop primarily desired to learn skills for home medical care. To this end, consecutively holding the workshop and a cooperation support system with other medical and care professionals would be indispensable.
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December 2014

[Opinions of and conscious changes in pharmacists who participated in home medical care training workshop:].

Gan To Kagaku Ryoho 2013 Dec;40 Suppl 2:159-60

We organized a home medical care training workshop to offer community pharmacists an opportunity to learn more about home medical care. The workshop consisted of lectures by the doctor, the nurse, and the pharmacist. A questionnaire was handed out to all the participants once the workshop had ended. On an average, the participants rated the overall quality of the workshop as 8.1 out of 10. Our results revealed that 62.7% of the participating pharmacists were experienced in home medical care, with the majority having between 1 and 5 years of experience. Most pharmacists with experience in home care had provided services such as delivering medicines to or instructing patients on the use of medicines at patient homes. Participants suggested that the qualities necessary for providing effective home medical care were knowledge of home-based care and a positive attitude, among others. Participants also made suggestions for lecture contents in future workshops, such as contract procedures or specific cases of home medical care. Furthermore, participants expressed many positive opinions such as the desire to hear the views of other professionals on home medical care. In conclusion, participation in the home medical care training workshop increased the participants' desire to learn and perform home medical care. This indicates that a subsequent workshop with the cooperation of other professionals is indispensable.
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December 2013

[Nutritional assessment employing the malnutrition universal screening tool for patients with colorectal cancer undergoing outpatient chemotherapy].

Gan To Kagaku Ryoho 2013 Sep;40(9):1185-8

Nutrition Support Team, Ikeda Municipal Hospital, Japan.

Objective: We surveyed the nutritional status of patients with colorectal cancer undergoing outpatient chemotherapy using the malnutrition universal screening tool(MUST)to examine its usefulness and association with adverse events.

Methods: We examined the use of the MUST and the incidences of adverse events in 34 patients with advanced or recurrent colorectal cancer who had undergone outpatient chemotherapy between April and December 2010.

Results: The high-risk patients requiring nutritional care intervention comprised 47. 1%(16 patients)of the study population, and these patients exhibited significant decreases in body weight and body mass index. The incidences of appetite loss and fatigue were significantly higher in the high-risk group than in the low-risk group.

Discussion: Precautions against adverse events may prevent a worsening of the nutritional status of patients with colorectal cancer. Thus, nutritional assessment is necessary in patients undergoing outpatient chemotherapy. Furthermore, the MUST appears to represent a very useful simplified nutritional screening method for the nutritional management for these patients.
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September 2013

[A questionnaire survey for pharmacists participating in a home medical care training workshop].

Gan To Kagaku Ryoho 2012 Dec;39 Suppl 1:70-3

Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University.

To clarify the issues associated with promoting pharmacists' participation in home medical care(HMC), we performed a questionnaire survey for pharmacists who participated in a HMC training workshop. The cumulative number of participants in the workshop was 284; the majority of the participants was from mid-sized pharmacies and had been working for over 10 years. The rate of pharmacists engaged in HMC was 69% and their main practices were "drug delivery to patients" and "drug administration guidance for patients at home". Many participants responded that the key items for HMC were "cooperation with people with different type of jobs", "a wide pharmaceutical knowledge", and "effective involvement with patients and their families". The present main issues regarding HMC were "low pharmaceutical care fees", "deficiency of pharmacists", and "insufficient collaboration with people with different type of jobs". In order to resolve these issues, it is necessary to construct a cooperation system with other medical and welfare-related societies and to continuously organize such workshop.
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December 2012

Application of terahertz absorption spectroscopy to evaluation of aging variation of medicine.

Anal Sci 2011 ;27(2):209-12

Nagahama Institute of Bio-science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.

The absorption spectra of three kinds of medicines both before and after the expiration date: Amlodin OD(®) (5 mg), Basen OD(®) (0.2 mg) and Gaster D(®) (10 mg) have been measured by terahertz time domain spectroscopy (THz-TDS). All the medicines show some differences in the THz absorption spectra between medicines before and after the expiration dates. X-Ray powder diffraction (XRD) studies of all medicines suggest that the polymorph of the main effective compound is not changed before and after the expiration date. Therefore, the differences in the THz spectra between medicines before and after the expiration dates arise from aging variation of diluting agents and/or from modifications of intermolecular interaction between the effective compounds and diluting agents.
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http://dx.doi.org/10.2116/analsci.27.209DOI Listing
July 2011

In vitro approaches to evaluate placental drug transport by using differentiating JEG-3 human choriocarcinoma cells.

Basic Clin Pharmacol Toxicol 2011 Feb 18;108(2):138-45. Epub 2010 Oct 18.

Osaka Ohtani University, Japan.

Human choriocarcinoma cells have been used as models for studying transcellular drug transport through placental trophoblasts. However, these models allow the transport of low-molecular-weight drugs through intercellular gap junctions. This study aimed at investigating the differentiation patterns of JEG-3 choriocarcinoma cells under different culture conditions and establishing the appropriate model of in vitro syncytiotrophoblast drug transport. Paracellular permeability was estimated by measuring the transepithelial electrical resistance (TEER) across JEG-3 cell layers. The mRNA expression levels of non-expressed in choriocarcinoma clone 1 (NECC1) and breast cancer resistance protein (BCRP), and those of E-cadherin (ECAD) and cadherin-11 (CDH11), which are adherens junction-associated proteins related to fusogenic ability of syncytiotrophoblasts differentiated from cytotrophoblasts, protein expression levels were considered as the differentiation signals. The highest TEER values were obtained in the JEG-3 cells cultured in the Dulbecco's modified Eagle's medium (DMEM)/Ham's F-12 (1:1) mixed medium (CS-C(®) ; Dainippon Sumitomo Pharma Co. Ltd., Osaka, Japan). By comparing the TEER values and the differentiation signals, the authors identified at least five JEG-3 cell-differentiation patterns. The differentiation pattern of JEG-3 cultured in CS-C resembled the syncytiotrophoblast-like differentiation signal characterizations in vivo. In conclusion, the syncytiotrophoblast-like models of differentiating JEG-3 cells cultured in CS-C might be appropriate for evaluating drug transport across the placental trophoblast.
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http://dx.doi.org/10.1111/j.1742-7843.2010.00634.xDOI Listing
February 2011

Reduction of opioid side effects by prophylactic measures of palliative care team may result in improved quality of life.

J Palliat Med 2010 Apr;13(4):401-6

Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka, Japan.

Purpose: In February 2002, the palliative care team was established in Ikeda Municipal Hospital to improve palliative care. We investigated changes in the incidences of side effects related to opioids, and evaluated palliative care team activities.

Methods: Regarding inpatients for whom narcotics were prescribed in our hospital in the years of 2002 (from October 1, 2002 until September 30, 2003), 2004 (from October 1, 2004 until September 30, 2005), and 2006 (from October 1, 2006 until September 30, 2007), we surveyed the rates at which laxatives or antiemetics were prescribed, frequency of defecation/its state before and after the start of narcotic therapy, frequency of nausea/vomiting, and dietary intake.

Results: The proportions of patients in whom laxatives were simultaneously prescribed during opioid therapy in 2002, 2004, and 2006 were 43.5%, 78.7%, and 75.6%, respectively. The proportions of those in whom antiemetics were combined with opioids were 45.7%, 78.7%, and 78.0%, respectively. The incidences of constipation were 50.0%, 39.3%, and 37.8%, respectively. Those of nausea/vomiting were 30.4%, 21.3%, and 9.8%, respectively. Those of anorexia were 65.3%, 39.4%, and 15.4%, respectively.

Conclusions: These results suggest that palliative care team activities facilitated appropriate drug prescription during opioid therapy, reducing the appearance of side effects, with likelihood of improved quality of life.
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http://dx.doi.org/10.1089/jpm.2009.0355DOI Listing
April 2010

Terahertz absorption spectra of original and generic ceftazidime.

Anal Sci 2009 Dec;25(12):1483-5

Nagahama Institute of Bio-science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.

The absorption spectra of ceftazidime and its generic versions (Modacin, Mosyl, and Mobenzocin) have been measured by terahertz time domain spectroscopy (THz-TDS). Differences in the THz absorption were observed between the original and generic versions. The results show small, but significant differences in the states of ceftazidime hydrate between the original and generic versions. THz-TDS can be used to evaluate the stability of medicines as well as to control their quality.
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http://dx.doi.org/10.2116/analsci.25.1483DOI Listing
December 2009
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