Lack of pharmacokinetic interaction between pilsicainide and rifampicin in healthy volunteers

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±0.06μg/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.