Shimoda K, Minowada T, Noguchi T, Takahashi S
Department of Psychiatry, Shiga University of Medical Science, Otsu, Japan.
J Clin Psychopharmacol. 1993 Jun;13(3):181-8.
We measured the concentrations of clomipramine and its metabolites, N-desmethylclomipramine, 8-hydroxy-N-desmethylclomipramine, and 8-hydroxyclomipramine in plasma in 92 Japanese psychiatric patients receiving clomipramine hydrochloride (Anafranil, Ciba-Geigy Japan Limited, Takarazuka, Japan) by high-performance liquid chromatography. Although there were large interindividual variations of total drug concentrations and concentrations of parent or intermediate metabolic compounds in plasma, significant positive correlations were observed between these drug concentrations and daily doses of clomipramine hydrochloride (milligrams per kilogram of body weight). The metabolic ratios for both desmethylation and hydroxylation varied substantially with 30- to 90-fold interindividual variations. Frequency distribution histograms and probit analyses of these parameters identified only one possible poor hydroxylator but no poor desmethylator of clomipramine. These results suggest that there are large interindividual variations of capacities for hydroxylation and desmethylation of clomipramine in the Oriental population and that therapeutic drug monitoring is essential in clinical practice to reduce the adverse effects of clomipramine and to prevent poor response to clomipramine.
我们采用高效液相色谱法，测定了92例接受盐酸氯米帕明（Anafranil，日本Takara生物株式会社）治疗的日本精神病患者血浆中氯米帕明及其代谢产物N-去甲基氯米帕明、8-羟基-N-去甲基氯米帕明和8-羟基氯米帕明的浓度。尽管血浆中总药物浓度以及母体或中间代谢化合物浓度存在较大的个体间差异，但这些药物浓度与盐酸氯米帕明每日剂量（毫克/千克体重）之间存在显著的正相关。去甲基化和羟基化的代谢率差异很大，个体间差异为30至90倍。这些参数的频率分布直方图和概率分析仅确定了1例可能的氯米帕明羟基化能力差的患者，但未发现去甲基化能力差者。这些结果表明，东方人群中氯米帕明的羟基化和去甲基化能力存在较大个体间差异，在临床实践中进行治疗药物监测对于减少氯米帕明的不良反应以及预防对氯米帕明反应不佳至关重要。
