Midha K K, Hawes E M, Hubbard J W, Korchinski E D, McKay G
College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.
J Clin Psychopharmacol. 1989 Feb;9(1):4-8.
Interpatient variation in response to therapy with antipsychotic drugs is a major problem. This study was designed to assess the extent of variation in disease-free subjects in whom known sources of variance were controlled as much as possible. The subjects were 32 healthy, nonsmoking males of European origin, aged 18-25 years, and weighing no more than +/- 15% from the ideal weight for height. After an overnight fast, each subject ingested 50 mg of chlorpromazine. Plasma samples were harvested over a 24-hour period during which the subjects were on a standardized, caffeine-free diet. Plasma levels of chlorpromazine were measured by gas-liquid chromatography-mass spectrometry. The results showed wide intersubject variation in all pharmacokinetic parameters including maximum concentration, area under the curve, and oral clearance. Furthermore, none of the data were normally distributed. For each pharmacokinetic parameter, the distribution was leptokurtotic and skewed. As a consequence, the geometric means provided better estimates of central tendency than the arithmetic means. It seems that a major proportion of intersubject variation is an inherent problem that cannot be accounted for by differences in race, diet, smoking habits, or concomitant drug ingestion.
抗精神病药物治疗的患者间反应差异是一个主要问题。本研究旨在评估在已知变异来源尽可能得到控制的无病受试者中的变异程度。受试者为32名健康、不吸烟的欧洲裔男性，年龄在18至25岁之间，体重不超过身高理想体重的±15%。经过一夜禁食后，每位受试者摄入50毫克氯丙嗪。在24小时内采集血浆样本，在此期间受试者采用标准化的无咖啡因饮食。氯丙嗪的血浆水平通过气液色谱 - 质谱法测定。结果显示，所有药代动力学参数（包括最大浓度、曲线下面积和口服清除率）在受试者间存在广泛差异。此外，所有数据均不呈正态分布。对于每个药代动力学参数，分布都是尖峰态且有偏态。因此，几何平均数比算术平均数能更好地估计集中趋势。似乎受试者间变异的主要部分是一个固有问题，无法用种族、饮食、吸烟习惯或同时摄入药物的差异来解释。
