Volz M, Mitrovic V, Schlepper M
Max Planck Institute for Physiological and Clinical Research, Kerckhoff-Klinik GmbH, Bad Nauheim, Germany.
Int J Clin Pharmacol Ther. 1994 Jul;32(7):370-5.
In a selected group of 86 patients (60 males, 26 females) with symptomatic ventricular arrhythmias, possible interactions between metabolic and chiral effects at steady-state were investigated by comparing the plasma levels of propafenone, its major metabolites and the 2 structural isomers. The antiarrhythmic drug propafenone is metabolized--besides a minor dealkylation pathway--mainly via 5-hydroxylation. It is a well-known phenomenon that this oxidative pathway is not shared by all individuals to the same extent. We were able to verify among our subjects the portion of so-called poor metabolizers reported in the literature for the total population. Propafenone was administered as a slow release formulation at 3 different dose regimens (2 x 225 mg, 2 x 325 mg and 2 x 425 mg). The crude drug is a racemic mixture of equal amounts of R- and S-forms. During treatment, the plasma S and R ratio was shifted towards the S-isomer due to preferential clearance of the R-form. It was further found that neither a genetic disposition (gender, metabolic phenotype) nor age or the dose applied had any influence on the measured plasma isomer ratio.
在一组选定的86例有症状性室性心律失常的患者（60例男性，26例女性）中，通过比较普罗帕酮及其主要代谢物和2种结构异构体的血浆水平，研究了稳态下代谢和手性效应之间的可能相互作用。抗心律失常药物普罗帕酮除了一条次要的脱烷基化途径外，主要通过5-羟基化代谢。众所周知，并非所有个体都以相同程度共享这种氧化途径。我们能够在我们的研究对象中验证文献报道的整个人口中所谓慢代谢者的比例。普罗帕酮以缓释制剂的形式按3种不同剂量方案（2×225毫克、2×325毫克和2×425毫克）给药。原料药是等量R型和S型的外消旋混合物。治疗期间，由于R型的优先清除，血浆S与R的比值向S异构体偏移。进一步发现，遗传倾向（性别、代谢表型）、年龄或所用剂量对测得的血浆异构体比值均无影响。
