摘要
目的 探讨反映氯氮平体内代谢的氯氮平药代动力学与反映细胞色素P45 0酶亚型1A2 (CYP1A2 )活性的咖啡因试验的相关性。方法 给 9名男性健康志愿者 (其中吸烟者 5名 )口服单剂量咖啡因 15 0mg后第 5h末采血 ;2天后口服单剂量氯氮平 10mg ,收集药代动力学设计的血样。结果 氯氮平的 0～ 2 4h药时曲线下面积 (AUC0 ,2 4)平均为 (2 6 8± 78) μg·h- 1 ·L- 1 ;半衰期平均为 (2 8± 10 )h ;达峰时间平均为 (2 1± 0 8)h。反映CYP1A2活性的咖啡因代谢产物次黄嘌呤 (17X)与咖啡因(137X)的比值 (17X 137X)与反映体内氯氮平清除的氯氮平AUC0 ,2 4的倒数呈显著正相关 (r=0 6 6 7,P <0 0 5 )。吸烟者的氯氮平AUC0 ,2 4[(2 2 4± 5 4) μg·h- 1 ·L- 1 ]低于非吸烟者 [(32 3± 70 ) μg·h- 1 ·L- 1 ],t=2 42 ,P <0 0 5。结论 CYP1A2酶活性与氯氮平体内代谢相关。CYP1A2在体内可能催化氯氮平的氧化代谢。吸烟可能诱导氯氮平的体内代谢。临床上合用其他影响CYP1A2活性的药物时应密切监测氯氮平血浓度。
Objective The study was to investigate the relationship between clozapine disposition and CYP1A2 activities by caffeine test Methods Nine male normal volunteers (5 smokers) took a single oral dose of 150 mg caffeine and plasma samples were collected at the end of 5th hour after administration of caffeine With a washout interval of two days, the subjects received a 10 mg single oral dose of clozapine Results The mean clozapine AUC 0,24 , t 1/2 , and T max , were (268±78) mg·h -1 ·L -1 , (28±10) h, and (2 1±0 8) h, respectively The indexes of CYP1A2 activities, by the ratios of paraxanthine (17X) and caffeine (137X) in plasma, were correlated with reciprocals of clozapine AUC 0,24 ( n =9, r =0 667, P <0 05) The clozapine AUC 0,24 of smokers were significantly lower than no smokers ( t =2 42, P <0 05) Conclusions It is suggested that CYP1A2 may be involved in clozapine disposition in vivo Smoking could induce the enzymes of clozapine metabolism Monitoring of clozapine plasma concentration is recommended in the patients treated at same time with other drugs affecting CYP1A2
出处
《中华精神科杂志》
CAS
CSCD
2000年第1期16-19,共4页
Chinese Journal of Psychiatry
