Shanghai Institute of Materia Medica and Graduate School, Chinese Academy of Sciences, 555 Zuchongzhi Rd., Shanghai 201203, PR China.
Drug Metab Dispos. 2010 May;38(5):817-23. doi: 10.1124/dmd.109.031328. Epub 2010 Feb 17.
Controversy exists concerning the sex-dependent differences in cytochrome P450 3A activity in humans. Meta-analysis of selected studies may address this question. Meta-analysis was performed on published or unpublished data in terms of sex-dependent differences in midazolam (MDZ) disposition in humans. The following pharmacokinetic parameters were included for the analysis: MDZ oral and systemic clearance, area under the concentration-time curve (AUC) of oral and intravenous MDZ, MDZ oral bioavailability (F), and MDZ gastrointestinal extraction (E(G)). Ten studies including 409 healthy volunteers were identified. Women exhibited 16% higher weight-corrected MDZ oral clearance (P < 0.001) and 20% higher systemic clearance (P = 0.002) than men. No significant difference in the AUC after oral dosing of MDZ was noted between sexes. Women showed lower AUC of intravenous MDZ than men (P = 0.02). No sex-dependent differences were observed in F and E(G). In conclusion, women showed significantly greater hepatic CYP3A activity than men, whereas no sex-dependent difference in intestinal CYP3A activity was observed.
关于人类细胞色素 P450 3A 活性的性别依赖性差异存在争议。对选定研究的荟萃分析可能会解决这个问题。根据人类咪达唑仑（MDZ）处置的性别依赖性差异，对已发表和未发表的数据进行了荟萃分析。分析中包括以下药代动力学参数：MDZ 口服和全身清除率、口服和静脉 MDZ 的浓度-时间曲线下面积（AUC）、MDZ 口服生物利用度（F）和 MDZ 胃肠道提取（E(G)）。确定了包括 409 名健康志愿者的 10 项研究。女性的 MDZ 口服清除率校正体重后比男性高 16%（P < 0.001），全身清除率高 20%（P = 0.002）。口服 MDZ 后，男女之间的 AUC 无显著差异。女性静脉注射 MDZ 的 AUC 低于男性（P = 0.02）。F 和 E(G) 没有观察到性别依赖性差异。总之，女性的肝 CYP3A 活性明显高于男性，而肠道 CYP3A 活性则没有性别依赖性差异。
