Lack of Pharmacokinetic Interaction between Pilsicainide and Rifampicin in Healthy Volunteers
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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)
- 一般社団法人 日本臨床薬理学会の論文
一般社団法人 日本臨床薬理学会 | 論文
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