Vozeh S, Haefeli W, Ha H R, Vlcek J, Follath F
Department of Medicine, University Hospital, Basel, Switzerland.
Eur J Clin Pharmacol. 1990;38(5):509-13. doi: 10.1007/BF02336693.
The pharmacokinetics of oral and i.v. propafenone and its major metabolites have been investigated in 8 healthy subjects. The total body clearance of propafenone was 963 ml/min, the terminal half-life 198 min and its absolute bioavailability was 15.5%. The two active metabolites (5-hydroxypropafenone and N-depropylpropafenone) showed non-linear kinetics in that both the dose-corrected area under the serum concentration-time curve and the amount excreted in the urine were larger after oral dosing. This resulted in considerably higher serum concentrations of the metabolites despite comparable serum concentrations of the parent compound. Thus, the concentration-effect relationship in the same patient may differ after oral and intravenous doses if concentrations of the active metabolite(s) are not taken into consideration. Although the mechanism of the nonlinearity is not clear, the data indicate that it may be due to saturable biliary excretion of the metabolites.
已在8名健康受试者中研究了口服和静脉注射普罗帕酮及其主要代谢产物的药代动力学。普罗帕酮的总体清除率为963毫升/分钟，终末半衰期为198分钟，其绝对生物利用度为15.5%。两种活性代谢产物（5-羟基普罗帕酮和N-去丙基普罗帕酮）表现出非线性动力学，即口服给药后血清浓度-时间曲线下的剂量校正面积和尿中排泄量均较大。尽管母体化合物的血清浓度相当，但这导致代谢产物的血清浓度显著更高。因此，如果不考虑活性代谢产物的浓度，同一患者口服和静脉给药后的浓度-效应关系可能会有所不同。虽然非线性的机制尚不清楚，但数据表明这可能是由于代谢产物的胆汁排泄饱和所致。
