臨床薬理

Pilsicainide, a class Ic antiarrhythmic agent, is a cationic compound. It has been hypothesized that a P-glycoprotein (P-gp)-induced transport mechanism may mediate the intestinal absorption and the renal excretion of pilsicainide. We evaluated whether rifampicin, a known inducer of P-gp, affects the pharmacokinetics of pilsicainide after oral dosing in healthy subjects. A pharmacokinetic study was conducted on 8 healthy male subjects (aged 30 ± 8 years; body weight 65.7 ± 6.5 kg) and demonstrated that rifampicin (450 mg given orally once daily for 4 days) did not significantly affect the maximum plasma concentration (pilsicainide alone: 0.39 ± 0.15 versus pilsicainide + rifampicin: 0.36 ± 0.06 μg/mL), the time to maximum plasma concentration (1.38 ± 0.83 versus 1.06 ± 0.18h), the area under the plasma concentration-time curve (2.81 ± 0.91 versus 2.58 ± 0.62 μg·h/mL), the renal clearance (198.46 ± 85.93 versus 194.34 ± 69.91 mL/min) or the net renal clearance by tubular secretion (128.75 ± 73.56 versus 119.93 ± 79.84 mL/min) of pilsicainide after a single oral dose (50 mg). In conclusion, our results indicated that rifampicin did not affect the pharmacokinetics of pilsicainide after oral dosing in humans. (Jpn J Clin Pharmacol Ther 2013; 44(4): 301-305)

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FENTANYL Tape for 3 days 2.1 mg 「MEIJI」(fentanyl M) is an adhesive preparation containing the same amount of fentanyl as Durotep^® MT Patch 2.1 mg (Janssen Pharmaceuticals, Inc.)(fentanyl D), and was jointly developed by Meiji Seika Pharma Co., Ltd. and Yutoku Pharmaceutical Ind. Co., Ltd. The present study was performed to investigate the safety and pharmacokinetics of fentanyl M in Japanese healthy male subjects when naltrexone was co-administered and to investigate the bioequivalence between fentanyl M and fentanyl D. In this open label, randomized, two-way cross-over study, transdermal fentanyl was applied to the subject's chest (period I: right, period II: left) as a single 72-hour application. We confirmed the safety and pharmacokinetics of fentanyl M in Japanese healthy male subjects co-administered naltrexone, and the bioequivalence between fentanyl D and fentanyl M. Safety was assessed up to 120 hours after a single application of fentanyl tape co-administered with naltrexone, and drug concentrations in serum samples were measured for calculation of pharmacokinetic parameters of fentanyl to determine bioequivalence. The safety and serum concentrations were comparable between fentanyl M and fentanyl D. The mean values of PK parameters (C_max, AUC_0→t, AUC_0→∞, MRT_0→t, MRT_0→∞, k_el, t_max and t_1/2) were comparable between the two products and 90% confidence intervals were within the predefined bioequivalence range. Fentanyl M is expected to have similar efficacy and safety as fentanyl D in patients with cancer pain. (Jpn J Clin Pharmacol Ther 2013; 44(4): 307-312)

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As the number of chronic kidney disease patients increases every year, a concomitant increase in drug use among patients with renal impairment is anticipated in daily clinical practice. For patient safety, drug information should be useful and meet the needs of medical workers. The aim of this study was to investigate the problem of the descriptions in package inserts of prescription drugs regarding: 1) drug administration to patients with renal impairment, and 2) effects of the drug on the kidney (hereinafter “information on renal function” ). Also, we evaluated the usefulness of the renal function information for medical workers. For this survey, 337 prescription drugs that require careful attention for use in patients with renal impairment were selected. We extracted “the information on renal function” described in the package inserts of these 337 prescription drugs from the website of Pharmaceuticals and Medical Devices Agency. We compared the contents of the information regarding the pharmacokinetics of patients with renal impairment described in the package insert with those described in the corresponding interview form. In 44.8% of the 337 package inserts, information on pharmacokinetics in patients with renal impairment was not included. Only 21.2% of the inserts contained useful information on drug administration to such patients, such as clear dose adjustment. Therefore, our survey suggests that the package inserts do not provide sufficient information on “renal function” for medical workers. In conclusion, improvement of the information regarding “renal function” in the prescription drug package inserts is necessary in order to meet the needs of medical workers. (Jpn J Clin Pharmacol Ther 2013; 44(4): 313-318)

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