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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 Z血浓度
Abstract：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.
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基本信息:
DOI：10.19577/j.cnki.issn10074406.2000.03.008
中图分类号:R96
引用信息:
[1]王传跃,欧阳东生,周宏灏,朱荣华,赵靖平,陈远光,杨德森.咖啡因试验与氯氮平体内代谢的相关性[J].中国临床药学杂志,2000(03):149-152.DOI:10.19577/j.cnki.issn10074406.2000.03.008.
2000-06-25
2000-06-25