Publications by authors named "Sachiyo Funakoshi"

6 Publications

  • Page 1 of 1

[Excretion Management During Colorectal Cancer Chemotherapy].

Gan To Kagaku Ryoho 2016 Aug;43(8):989-93

Dept. of Pharmacy, Kansai Rosai Hospital.

There are almost no reports about drug excretion management during colorectal cancer chemotherapy. Anticancer chemotherapeutic drugs excreted in urine and feces may exert toxic effects and promote teratogenesis, mutagenesis, and carcinogenesis. To assess the knowledge of patients about drug excretion, a questionnaire survey was performed among 45 patients receiving chemotherapy for colorectal cancer in our hospital; among them, 36 patients completed the survey. Most of the patients did not know about the excretion and toxic effects of anticancer drugs. The results indicate that patients should be instructed on the management ofexcretion during chemotherapy to minimize toxic exposure. We believe that unnecessary exposure of patients and their families to anticancer drugs should be minimized. This study highlights the importance of issuing guidelines regarding excretion management during cancer chemotherapy.
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August 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

Role of organic anion transporting polypeptide 2 in pharmacokinetics of digoxin and beta-methyldigoxin in rats.

J Pharm Sci 2005 Jun;94(6):1196-203

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.

Recently, we found that potent P-glycoprotein (P-gp) inhibitors, such as verapamil and cyclosporin A, markedly modulated the pharmacokinetics of digoxin in rats, whereas they did not affect beta-methyldigoxin pharmacokinetics significantly. Digoxin is also a substrate of rat organic anion transporting polypeptide 2 (Oatp2). Here, we compared the magnitude of Oatp2-mediated drug interaction of digoxin and beta-methyldigoxin using amiodarone as an Oatp2 inhibitor in rats. Amiodarone (20 mg/kg) given intravenously significantly increased plasma levels and decreased biliary excretion, liver distribution, and intestinal distribution of digoxin administered intravenously at a dose of 10 mug/kg. Amiodarone also significantly decreased biliary excretion and liver distribution of beta-methyldigoxin, but the change in plasma levels of beta-methyldigoxin was quite small. These findings may give a clue in selecting these cardiac glycosides in clinical pharmacotherapy for patients receiving multiple drugs towards escape from Oatp2-mediated drug interactions.
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http://dx.doi.org/10.1002/jps.20346DOI Listing
June 2005

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

Role of P-glycoprotein in pharmacokinetics and drug interactions of digoxin and beta-methyldigoxin in rats.

J Pharm Sci 2003 Jul;92(7):1455-63

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.

Digoxin and beta-methyldigoxin were evaluated pharmacokinetically in terms of P-glycoprotein (P-gp)-mediated drug interactions in rats. Evaluation was made by measuring the effects of a potent P-gp inhibitor (verapamil, cyclosporin A) on in vitro efflux transport of these compounds across the everted small intestine, on in situ absorption from the small intestine, and on in vivo total plasma clearance (CL(total)) as well as biliary and urinary excretions after intravenous administration. Both the intestinal efflux transport and absorption of beta-methyldigoxin were approximately 1.5-fold greater than those of digoxin, probably due to its higher lipophilicity. Addition of verapamil (300 microM) significantly decreased the intestinal efflux transport and increased the intestinal absorption of digoxin. In contrast, the influence of verapamil on beta-methyldigoxin was small. Intravenous cyclosporin A (30 mg/kg) significantly decreased in vivo CL(total) and biliary excretion of digoxin, but affected little on beta-methyldigoxin clearances. These results suggest that P-gp-mediated drug interactions can easily occur in digoxin, but hardly in beta-methyldigoxin. These findings may give a clue in selecting these digitalis compounds in clinical use, towards escape from P-gp-mediated drug interactions or reduction of interindividual variations.
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http://dx.doi.org/10.1002/jps.10416DOI Listing
July 2003

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
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