Midha K K, Hawes E M, Hubbard J W, Korchinski E D, McKay G
College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.
Psychopharmacology (Berl). 1988;96(2):206-11. doi: 10.1007/BF00177561.
The single dose pharmacokinetics of fluphenazine (2 x 5 mg tablets, Prolixin) were studied in 21 drug free male psychiatric patients (12 black, 9 white). Plasma samples were harvested over a period of 48 h while the patients were on a strictly controlled diet. The results showed wide interpatient variations in all pharmacokinetic parameters including Cmax, AUC, apparent oral clearance, and elimination half-life. It was determined for each of these parameters that the geometric mean gave a better estimate of central tendency than the corresponding arithmetic mean and the distribution was skewed and leptokurtotic. There was no significant difference between blacks and whites in any pharmacokinetic parameter examined. Considerable variations and marked undulations in the elimination portion of the plasma concentration versus time profiles were evident, possibly indicating biliary recycling of the drug. These undulations made it difficult to determine elimination rate constants for several of the patients. Hydrolysis or plasma samples from one patient demonstrated that the conjugate(s) of fluphenazine was present in three to four times the concentration of the unchanged drug.
在21名未服用药物的男性精神病患者（12名黑人，9名白人）中研究了氟奋乃静（2片5毫克片剂，Prolixin）的单剂量药代动力学。在患者严格控制饮食的48小时内采集血浆样本。结果显示，包括Cmax、AUC、表观口服清除率和消除半衰期在内的所有药代动力学参数在患者间存在很大差异。对于这些参数中的每一个，均确定几何平均数比相应的算术平均数能更好地估计集中趋势，且分布呈偏态和尖峰态。在所检查的任何药代动力学参数中，黑人和白人之间均无显著差异。血浆浓度-时间曲线消除部分存在相当大的变化和明显波动，这可能表明药物存在胆汁循环。这些波动使得难以确定几名患者的消除速率常数。对一名患者的水解或血浆样本显示，氟奋乃静的结合物浓度是未变化药物浓度的三到四倍。
