Publications by authors named "Yorinobu Maeda"

12 Publications

  • Page 1 of 1

Study on the infusion-site adverse events and vascular distribution of epirubicin in chemotherapy with epirubicin and fosaprepitant.

Mol Clin Oncol 2019 Jul 24;11(1):43-49. Epub 2019 Apr 24.

Laboratory of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmaceutical Sciences, Hiroshima International University, Kure, Hiroshima 737-0112, Japan.

In breast cancer patients on a fluorouracil-epirubicin (EPI)-cyclophosphamide (FEC) regimen and intravenous fosaprepitant (FAP) during chemotherapy, infusion-site adverse events such as vascular pain and induration and/or phlebitis are observed. In the present study, adverse events induced by the FEC regimen and FAP, a prodrug of aprepitant (AP), were studied based on the vascular tissue distribution of EPI in rats. Rats were treated with intravenous FAP (3 mg/kg, 10 min-constant rate infusion) or oral AP (3 mg/kg) and then intravenous EPI (1 mg/kg, 5 min-constant rate infusion) as follows: FAP-S Group, FAP and then EPI was infused from the same site on the jugular vein; FAP-D Group, FAP and then EPI was infused from different jugular veins (left and right); and AP Group, AP was administered orally and EPI was infused from the jugular vein. Concentrations of EPI in vascular tissue at the EPI infusion sites and opposite sites of the jugular vein (left and right, respectively) were measured at 30 min and 24 h after EPI infusion. Histological observation of the EPI infusion site was also made separately. In rats, the tissue concentrations of EPI at the infusion site in the FAP-S group were higher than those in the FAP-D and AP groups. Inflammation and necrosis were observed at the EPI infusion-site vascular tissue of the FAP-S group, but not of the FAP-D and AP groups. These findings could aid the development of an approach to avoid infusion-site adverse events in anthracycline-based chemotherapy in the clinical practice.
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http://dx.doi.org/10.3892/mco.2019.1849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535639PMC
July 2019

Reduction in the rate of postoperative delirium by switching from famotidine to omeprazole in Japanese hepatectomized recipients.

J Pharm Health Care Sci 2019 7;5:10. Epub 2019 May 7.

Department of Pharmacy, Chugoku Rosai Hospital, 1-5-1 Hiro-tagaya, Kure, Hiroshima, 737-0193 Japan.

Background: Hepatectomy is a highly invasive procedure with a high probability of postoperative delirium. Treatment with antiulcer drugs is indispensable after hepatectomy for anastomotic ulcer management. The clinical pathway for hepatectomy was reviewed and the antiulcer drug used was switched from famotidine, a H-receptor antagonist, to omeprazole, a proton pump inhibitor, owing to the pharmacist's intervention.

Methods: Hepatectomized recipients over 65 years of age, except in the cases of laparoscopic surgery and intensive care unit entry, were treated with famotidine injections (10 patients) or omeprazole injections (11 patients), and the incidence rates and severity of delirium were compared between the famotidine and omeprazole groups. The delirium after hepatectomy was assessed using the Japanese version of the NEECHAM confusion scale.

Results: The incidence rates of delirium were 90% in the famotidine group and 27.3% in the omeprazole group. Four out of 9 recipients in the famotidine group were injected with haloperidol to treat for delirium, but no recipients needed this treatment in the omeprazole group.

Conclusions: Compared with famotidine, the use of omeprazole was found to be effective in reducing the incidence rate and severity of postoperative delirium in patients undergoing hepatectomy. Pharmacists should actively strive to mitigate the risks of delirium.
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http://dx.doi.org/10.1186/s40780-019-0139-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505269PMC
May 2019

Dosage Adjustment of Dabigatran Etexilate Based on Creatinine Clearance in Patients With Cardioembolic Stroke or Atrial Fibrillation.

Ther Drug Monit 2016 12;38(6):670-676

*Department of Pharmacy, Chugoku Rosai Hospital; and †Laboratory of Biopharmaceutics and Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Hiroshima International University, Kure, Japan.

Background: A recommendation for dosage adjustment of dabigatran etexilate, a prodrug of dabigatran, seems to be desirable based on creatinine clearance to avoid bleeding and stroke.

Methods: Outpatients and inpatients having a history of cardioembolic stroke or atrial fibrillation were included. After taking dabigatran etexilate orally (75-150 mg twice daily) for at least 1 week, plasma trough concentration (Ctrough, ng/mL) of dabigatran and creatinine clearance (CLcr, mL/min) of patients according to Cockcroft and Gault equation were determined.

Results: Among the 38 patients studied, Ctrough of dabigatran and CLcr were scattered in a range from 31.4 to 329.5 ng/mL and 15.4-133.4 mL/min, respectively. Temporal CLtotal (Temp-CLtotal) of dabigatran, estimated by dividing the daily absorbed amount of dabigatran etexilate with Ctrough of dabigatran, was linearly correlated with CLcr of patients (P = 0.0018). Based on the findings, the daily dose of dabigatran etexilate that provides Ctrough of dabigatran at approximately 70 ng/mL was estimated.

Conclusions: A linear relationship was found between Temp-CLtotal of dabigatran and CLcr of patients. Depending on CLxr of patients, we recommend 4 different dosages of dabigatran etexilate to obtain Ctrough of dabigatran at approximately 70 ng/mL.
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http://dx.doi.org/10.1097/FTD.0000000000000336DOI Listing
December 2016

Interaction of magnesium oxide with gastric acid secretion inhibitors in clinical pharmacotherapy.

Eur J Clin Pharmacol 2014 Aug 13;70(8):921-4. Epub 2014 May 13.

Department of Pharmacy, Chugoku Rosai Hospital, 1-5-1 Hiro-Tagaya, Kure, Hiroshima, 737-0193, Japan,

Purpose: Magnesium oxide (MgO), a short-term osmotic laxative, is converted into MgCl2 under acidic condition in the stomach and then Mg(HCO3)2 in the intestinal tract, where Mg(HCO3)2 induces the water exudation into the intestine. This indicates that the laxative effect of MgO could be attenuated under the suppressed gastric acid secretion. In this study, the possible interaction of MgO with gastric acid secretion inhibitors was evaluated by using electronic patient records of MgO dosage levels.

Methods: Defecation was controlled with MgO alone in some patients after colon surgery (n = 67) and after total gastric resection (n = 4). Some other patients were treated with a combination use of MgO and H2 receptor antagonist (H2RA) (n = 14) or proton pump inhibitor (PPI) (n = 27). The possible drug interaction of MgO with H2RA or PPI was evaluated by comparing dosage levels of MgO used in controlling defecation.

Results: In controlling defecation, the daily dosage levels of MgO in patients taking H2RA or PPI and patients with total gastric resection were significantly higher than those patients taking MgO alone after colon surgery. The ratios of good constipation control (controlled well at the dosing level of 1,000 mg MgO) in patients taking H2RA or PPI were significantly lower than that in patients treated with MgO alone. In an in vitro study, the solubility of MgO at pH 4.5 was quite low, as compared with that at pH 1.2.

Conclusions: When patients received H2RA or PPI, the laxative effect of MgO is decreased possibly due to the low solubility of MgO at the higher gastric pH and less generation of MgCl2 and Mg(HCO3)2. Higher dosing level of MgO or another laxative should be used in patients taking H2RA or PPI, as well as the case of patients with total gastric resection.
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http://dx.doi.org/10.1007/s00228-014-1694-xDOI Listing
August 2014

Usefulness of one-point plasma SN-38G/SN-38 concentration ratios as a substitute for UGT1A1 genetic information after irinotecan administration.

Int J Clin Oncol 2014 Apr 19;19(2):397-402. Epub 2013 Apr 19.

Department of Pharmacy, Osaka Rosai Hospital, 1179-3 Nagasone-cho, Kita-ku, Sakai, Osaka, 591-8025, Japan.

Background: It was recently reported that genetic polymorphisms of UDP glucuronyltransferase-1 polypeptide A1 (UGT1A1), a glucuronidation enzyme, were associated with irinotecan (CPT-11) metabolism. The active metabolite of CPT-11, 7-ethyl-10-hydroxycamptothecin (SN-38) was glucuronidated (SN-38G) by UGT1A1. Genetic polymorphisms of UGT1A1 were associated with potentially serious adverse events, including neutropenia. Several studies have suggested that the dose of CPT-11 should be decreased in patients homozygous for UGT1A1*6 or UGT1A1*28, or double heterozygotes (*6/*28). However, the reference dose for patients with these genetic polymorphisms is unclear.

Methods: We investigated the relationship between the SN-38G/SN-38 concentration ratio and the dose of CPT-11 in 70 patients with colorectal cancer who received FOLFIRI-based regimens, by measuring the plasma concentrations of CPT-11, SN-38, and SN-38G.

Results: The SN-38G/SN-38 concentration ratio was lower in patients who were homozygous for UGT1A1*6, heterozygous for UGT1A1*6 or UGT1A1*28, or were double heterozygotes compared with patients with wild-type genes. The relative decreases in the SN-38G/SN-38 concentration ratio in patients homozygous for UGT1A1*6 and in double heterozygotes were greater than in patients heterozygous for UGT1A1*6 or UGT1A1*28. Interestingly, decreases in the SN-38G/SN-38 concentration ratio were associated with decreases in the neutrophil count and the final infusion dose of CPT-11.

Conclusion: Our results suggest that the SN-38G/SN-38 concentration ratio is an important factor for guiding dose adjustments, even in patients with wild-type genes. Therefore, the SN-38G/SN-38 concentration ratio, as an index of the patient's metabolic capacity, is useful for assessing dose adjustments of CPT-11.
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http://dx.doi.org/10.1007/s10147-013-0558-1DOI Listing
April 2014

Correlation between plasma concentration ratios of SN-38 glucuronide and SN-38 and neutropenia induction in patients with colorectal cancer and wild-type UGT1A1 gene.

Oncol Lett 2012 Mar 22;3(3):694-698. Epub 2011 Dec 22.

Department of Pharmacy, Osaka Rosai Hospital, Sakai, Osaka 591-8025.

In irinotecan (CPT-11)-based chemotherapy, neutropenia and diarrhea are often induced. In the present study, the clinical significance of the concentration ratios of 7-ethyl-10-hydroxycamptothecin (SN-38) glucuronide (SN-38G) and SN-38 in the plasma in predicting CPT-11-induced neutropenia was examined. A total of 17 patients with colorectal cancer and wild-type UDP-glucuronosyltransferase (UGT)1A1 gene were enrolled and treated with CPT-11 as part of the FOLFIRI regimen [CPT-11 and fluorouracil (5-FU)]. Blood was taken exactly 15 min following a 2-h continuous infusion of CPT-11. Plasma concentrations of SN-38, SN-38G and CPT-11 were determined by a modified high-performance liquid chromatography (HPLC) method. The median, maximum and minimum values of plasma SN-38G/SN-38 ratios were 4.25, 7.09 and 1.03, respectively, indicating that UGT activities are variable among patients with the wild-type UGT1A1 gene. The plasma SN-38G/SN-38 ratios decreased with an increase in the trial numbers of chemotherapy (r=0.741, p=0.000669), suggesting that CPT-11 treatment suppresses UGT activity, and the low plasma SN-38G/SN-38 ratios resulted in the induction of greater neutropenia. However, in this analysis, 2 clearly separated regression lines were observed between plasma SN-38G/SN-38 ratios and neutropenia induction. In conclusion, UGT activity involved in SN-38 metabolism is variable among patients with the wild-type UGT1A1 gene, and each CPT-11 treatment suppresses UGT activity. One-point determination of the plasma SN-38G/SN-38 ratio may provide indications for the prediction of CPT-11-induced neutropenia and adjustment of the optimal dose, although further studies are required.
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http://dx.doi.org/10.3892/ol.2011.533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362497PMC
March 2012

Evaluation of clinical efficacy of Maeda's nomogram for vancomycin dosage adjustment in adult Japanese MRSA pneumonia patients.

Drug Metab Pharmacokinet 2006 Feb;21(1):54-60

Department of Pharmacy, Okayama Rousai General Hospital, Japan.

The clinical efficacy of Maeda's nomogram for vancomycin dosage adjustment was evaluated by comparison with a standard dosage regimen (package insert information: vancomycin dose reduced in elderly patients and patients with renal dysfunction, with Moellering's nomogram used for renal-dysfunction patients) in adult Japanese MRSA pneumonia patients. Using Maeda's nomogram, the vancomycin dose is fixed at 1,000 mg while the dosing interval is varied in accordance with individual creatinine clearance. Using a standard dosage regimen, 5 patients out of 27 (18.5%) achieved target plasma levels of vancomycin (25-40 microg/mL for peak and 5-15 microg/mL for trough) within 2-6 days. Using Maeda's nomogram, 38 patients out of 53 (71.7%) achieved target levels in that time. A higher clinical response (complete resolution of all signs and symptoms of MRSA infection) to vancomycin therapy was also obtained with Maeda's nomogram when evaluated approximately 2-weeks after discontinuation of vancomycin therapy (43.4% versus 18.5% for the standard regimen). In conclusion, the Maeda's nomogram regimen with a 1,000 mg vancomycin dose was shown to achieve target plasma levels of vancomycin at a higher rate and provide higher clinical efficacy in vancomycin therapy of MRSA pneumonia patients, as compared with the currently available standard dosage regimen.
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http://dx.doi.org/10.2133/dmpk.21.54DOI Listing
February 2006

Increased erythrocyte distribution of valproic acid in pharmacokinetic interaction with carbapenem antibiotics in rat and human.

J Pharm Sci 2005 Aug;94(8):1685-93

Department of Pharmaceutics and Therapeutics, Programs for Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.

Carbapenem antibiotics cause pharmacokinetic interaction with valproic acid (VPA) in clinical pharmacotherapy. Here, we investigated the mechanism of interaction from the viewpoint of erythrocyte distribution of VPA in rats and humans. Imipenem or panipenem was administered intravenously and then VPA intravenously or into the intestinal lumen in rats. Both imipenem and panipenem significantly decreased plasma VPA levels. In contrast, these antibiotics did not affect, or rather increased, VPA levels in whole blood, and increased the erythrocyte distribution of VPA in vivo. In clinical, two patients receiving VPA were given imipenem intravenously, because of intractable infectious diseases. Imipenem lowered plasma VPA levels by approximately 40%-60% of original levels, and increased the erythrocyte distribution of VPA, as observed in rats. In conclusion, the pharmacokinetic interaction between VPA and carbapenem antibiotics, in which plasma VPA levels were markedly reduced, may partly be derived from the increased erythrocyte distribution of VPA.
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http://dx.doi.org/10.1002/jps.20338DOI Listing
August 2005

Prevention of irinotecan-induced diarrhoea by oral carbonaceous adsorbent (Kremezin) in cancer patients.

Oncol Rep 2004 Sep;12(3):581-5

Department of Pharmacy, Chugoku-Rousai General Hospital, 1-5-1 Hiro-Tagaya, Kure City, Hiroshima 737-0193, Japan.

Irinotecan (CPT-11) treatments induce severe diarrhoea at a rate of >40%. In clinical trials, we evaluated the preventing effects of oral alkalization, which has been reported previously, and oral carbonaceous adsorbent (Kremezin trade mark ) on diarrhoea possibly induced by CPT-11. Evaluation was made by counting the maximum number of bowel motions in each patient. Five patients out of 7 treated with CPT-11 had bowel motions of >5 times daily, and maximum number of bowel motions reached 20 times in 1 patient. Oral alkalization (2 g sodium bicarbonate, 2 g magnesium oxide and 300 mg ursodeoxycholic acid daily for 4 days) decreased bowel motions from 20 to 8 thereafter in the patient. Maximum number of bowel motions in other 3 patients treated in a combination of CPT-11 and oral alkalization was <3. Oral adsorbent (2 g Kremezin x 3 times, during and after CPT-11 treatment) also decreased maximum number of bowel motions from 7 (without oral adsorbent) to 3 in 1 patient. Also, the maximum number of bowel motions in other 3 patients treated with oral adsorbent was <3 (p<0.05, vs CPT-11 alone). Effect of oral Kremezin on plasma concentrations of CPT-11 and its related compounds after a 1-h CPT-11 infusion, evaluated in a patient, was small. These results suggested that the oral Kremezin is effective in ameliorating CPT-11-induced diarrhoea without decreasing much the plasma clearance of CPT-11.
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September 2004

Dosage adjustment of ribavirin based on renal function in Japanese patients with chronic hepatitis C.

Ther Drug Monit 2004 Feb;26(1):9-15

Department of Pharmacy, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.

The daily dose of ribavirin is currently determined based on body weight. In the present study, the authors examined factors influencing total plasma clearance (CL(total)) and the toxic level on red blood cells of ribavirin in such body weight-based dosage adjustment in Japanese chronic hepatitis C patients (13 male and 6 female). Patients received ribavirin (600 or 800 mg/d) orally, depending on their body weights, together with interferon alpha-2b (6 million units) intramuscularly. A steady-state trough plasma concentration (C(pss)) was achieved approximately 4 weeks after the initiation of treatment, but the value was scattered among patients in a range from 1100 to 4200 ng/mL. The high C(pss) of ribavirin of approximately 4000 ng/mL decreased hemoglobin concentrations to less than 8.5 g/dL. The individual CL(total), estimated by dividing dose normalized by body weight by C(pss), of ribavirin correlated significantly with the patient's creatinine clearance. In contrast, no relationship was observed with other parameters such as age, body weight, serum creatinine concentration, alanine aminotransferase (ALT) concentration, or aspartate aminotransferase (AST) concentration, though ALT and AST concentrations decreased with ribavirin treatment in most patients. These results indicate that CL(total) of ribavirin is dependent on renal function (creatinine clearance), and hemolysis is induced by high ribavirin concentrations in plasma. Dosage adjustment of ribavirin based on renal function and body weight would provide effective and safer treatment without causing hemolysis.
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http://dx.doi.org/10.1097/00007691-200402000-00004DOI Listing
February 2004

Possible mechanism for pharmacokinetic interaction between lidocaine and mexiletine.

Clin Pharmacol Ther 2002 May;71(5):389-97

Department of Pharmacy, Chugoku Rousai Hospital, 1-5-1 Hiro-Tagaya, Kure City, Hiroshima 737-0193, Japan.

Objective: Our objective was to elucidate the mechanism of pharmacokinetic interaction between lidocaine and mexiletine, because an unexpected increase in plasma lidocaine concentration accompanied by severe side effects was observed when mexiletine was administered to a patient with dilated cardiomyopathy.

Methods: Plasma concentrations of lidocaine, its major metabolites, and mexiletine were measured in a patient with dilated cardiomyopathy. The lidocaine-mexiletine interaction was evaluated by examination of the effects of mexiletine on plasma concentration and the tissue distribution of lidocaine in rabbits in vivo, as well as on the in vitro lidocaine binding to phosphatidylserine, a binding constituent for weakly basic drugs.

Results: Plasma lidocaine concentrations increased significantly when the oral dose of mexiletine was increased. This pharmacokinetic interaction was not attributable to a metabolic interaction as evaluated by plasma lidocaine metabolites concentrations. In rabbits, mexiletine seemed to decrease the total plasma clearance of lidocaine, resulting in increased plasma lidocaine concentrations. Mexiletine significantly reduced the tissue distribution of lidocaine to the kidneys and lungs. A strong displacing effect of mexiletine on the binding of lidocaine to phosphatidylserine was observed in vitro.

Conclusions: A drug interaction derived from the displacement of lidocaine from tissue binding sites by mexiletine that resulted in the increased plasma lidocaine concentrations was shown. This observation had implications for loading doses and acute effects of lidocaine in the concurrent therapy of lidocaine and mexiletine.
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http://dx.doi.org/10.1067/mcp.2002.124077DOI Listing
May 2002