摘要
目的 探讨细胞色素P450 1A2酶 (CYP1A2 )抑制剂氟伏沙明对奥氮平在体内代谢的影响。方法 1 2名男性健康志愿者 ,采用自身前后对照设计 ,两次服药间隔 4周 ,口服单剂奥氮平 1 0mg;对照部分采用单剂量奥氮平 ,试验部分是在氟伏沙明连续 9天服用过程中的第 4天合用单剂量奥氮平。高效液相色谱电化学法测定奥氮平血浆浓度。结果 合用氟伏沙明后 ,奥氮平各时点的平均浓度增高 ;奥氮平的峰浓度由 1 9 5μg/L增至 2 9 1 μg/L(1 52倍 ,P <0 0 0 1 ) ,消除半衰期由 32 2h延长为46 1h(1 48倍 ,P <0 0 1 ) ,0～ 1 2 0h药时曲线下面积由 647 5μg·h 1 ·L 1 增至 1 0 55 0 μg·h 1 ·L 1 (1 65倍 ,P <0 0 0 1 ) ;而达峰时间由 3 8h缩短为 2 6h(0 69倍 ,P <0 0 1 ) ,系统清除率由 1 6 4L/h减至 8 5L/h(0 59倍 ,P <0 0 0 1 ) ,表观分布容积由 435 5L降为 2 99 2L(0 70倍 ,P <0 0 1 )。结论 氟伏沙明能明显抑制奥氮平在体内的代谢。CYP1A2可能是催化奥氮平体内代谢的主要氧化酶之一。奥氮平与涉及CYP1A2的药物合用时应注意密切观察。
Objective The aim of the present study was to assess the possible effect of the CYP1A2 inhibitor fluvoxamine on the disposition of olanzapine in vivo Methods Twelve male volunteers were enrolled in the study They were assigned to two sessions with a drug free interval of at least 4 weeks All subjects received a single oral dose of olanzapine 10 mg In the control session the drug was taken alone, while in the concomitant fluvoxamine session olanzapine was administered on the 4th day of a 9 day treatment with fluvoxamine The plasma concentrations of olanzapine were detected by HPLC ECD Results After the co administration with fluvoxamine, mean olanzapine concentrations in plasma were increased throughout all sampling points Compared with the control session, concomitant fluvoxamine intake was associated with increased olanzapine C max (from 19 5 to 29 1 μg/L, P <0 001), a prolongation in olanzapine t 1/2 (from 32 2 to 46 1 hours, P <0 01), increased olanzapine AUC 0,120 (from 647 5 to 1 055 0 μg·h 1 ·L 1 , P <0 001); however, the olanzapine T max (from 3 8 to 2 6 hours, P <0 01), Cl s (from 16 4 to 8 5 L/h, P <0 001) and V d (from 435 5 to 299 2 L, P <0 01) were significantly reduced Conclusions Fluvoxamine markedly inhibits the metabolism of olanzapine in vivo CYP1A2 may be one of the major oxidative enzymes for the disposition of olanzapine in vivo It is recommended that the close observation and the benefit risk evaluation should be paid when the CYP1A2 involved drug is combined with olanzapine therapy
出处
《中华精神科杂志》
CAS
CSCD
北大核心
2003年第1期3-6,共4页
Chinese Journal of Psychiatry
基金
北京卫生扶持学科基金资助项目(无编号 )
首都医学发展科研基金资助项目 (ZD199816 )
