摘要
目的 :通过检测尿中咖啡因 ( Caf)及其代谢产物 ,探讨细胞色素 P45 0 1A2 ( CYP1A2 )与体内氯氮平 ( CL Z)去甲基代谢物的关系。方法 :单剂 po Caf15 0 mg,h5末采取尿样 ;以 Caf代谢产物和 Caf的比值 [( 17X+17U) / 137X]反映 CYP1A2活性。2 d后单剂 po CL Z10 m g,收集 0～ 2 4h尿样。 0～ 2 4h尿中 CL Z剩余量占给药剂量的百分率 ( CL Z% )反映 CL Z清除 ;0～ 2 4h尿中去甲氯氮平 ( DCL Z)生成量占 CL Z给药剂量的百分率 ( DCL Z% )反映 DCL Z生成。结果 :在 12例男性健康志愿者中 ,尿中 Caf代谢比值 [( 17X+17U) / 137X]与 0～ 2 4h尿中 DCL Z生成回收百分比 DCL Z% ( n=12 ,r=0 .6 99,P<0 .0 5 )呈显著性正相关 ,但与 0～ 2 4h尿中 CL Z剩余回收百分比 CL Z% ( n=12 ,r=0 .46 2 ,P>0 .0 5 )不相关。吸烟者的 Caf代谢比值显著高于非吸烟者 ( t=2 .48,P<0 .0 5 )。结论 :CYP1A 2在体内可能是通过介导 DCL Z的生成来参与 CL Z的清除。在合用其他影响CYP1A2活性的药物时有必要密切监测 CL
AIM: To investigate the correlation between clozapine (CLZ) demethylation and CYP1A2 enzyme activity by a caffeine (Caf) test in vivo. METHODS: Twelve male healthy volunteers were enrolled in the study. At the h 5 after a single oral dose of Caf 150 mg taken, urinary samples were collected. With a washout interval of 2 d, the subjects received a single oral dose of CLZ 10 mg, and 0-24 h urine was collected. CLZ elimination was assessed by the percentage of the dose of CLZ excreted as the drug in urine (CLZ%). The formation of demethylclozapine (DCLZ) was evaluated by the percentage of the dose of CLZ excreted as DCLZ in urine (DCLZ%). RESULTS: The ratio of Caf metabolism in urine, (paraxanthine + 1,7dimethyluric acid)/Caf, was significantly correlated with DCLZ% (n=12, r=0699, P< 005), but not with CLZ% (n=12, r=0462, P>005). The ratio of Caf metabolism in smokers was significantly higher than in nonsmokers (t=248,P<005). CONCLUSION: CYP1A2 may be involved in the demethylation of CLZ in vivo. Close monitoring of CLZ plasma concentration is recommended in patients treated at same time with other drugs affecting CYP1A2.
出处
《中国临床药学杂志》
CAS
2000年第3期149-152,共4页
Chinese Journal of Clinical Pharmacy
