Brøsen K, Davidsen F, Gram L F
Department of Clinical Pharmacology, Odense University, Denmark.
Br J Clin Pharmacol. 1990 Feb;29(2):248-53. doi: 10.1111/j.1365-2125.1990.tb03628.x.
The kinetics at a single oral dose (400 mg) of quinidine were studied in four extensive metabolizers (EM) and four poor metabolizers (PM) of sparteine. The clearance of quinidine by 3-hydroxylation was significantly lower in PM than in EM, but the difference was small (25-30%). This finding suggests that 3-hydroxylation, in part, is catalyzed by the same isoenzyme of cytochrome P450, P450db1 which oxidizes sparteine. Otherwise, no significant phenotypic differences in total or metabolic clearance were found and it is concluded that the metabolism of quinidine is largely carried out by P450 isoenzymes different from P450db1. A biexponential decline in the log plasma quinidine concentration vs time curves was observed in all subjects, and the mean elimination half-life was 11-12 h. This is about twice as long as generally reported in the literature.
在4名司巴丁广泛代谢者（EM）和4名司巴丁慢代谢者（PM）中研究了单次口服剂量（400毫克）奎尼丁的动力学。PM中通过3-羟基化的奎尼丁清除率显著低于EM，但差异较小（25%-30%）。这一发现表明，3-羟基化部分是由氧化司巴丁的细胞色素P450同一种同工酶P450db1催化的。否则，在总清除率或代谢清除率方面未发现显著的表型差异，得出的结论是奎尼丁的代谢主要由不同于P450db1的细胞色素P450同工酶进行。在所有受试者中均观察到血浆奎尼丁浓度对数与时间曲线呈双指数下降，平均消除半衰期为11-12小时。这大约是文献中一般报道时间的两倍。
