Sex-dependent differences in cytochrome P450 3A activity as assessed by midazolam disposition in humans: a meta-analysis.
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 Meta-analysis was performed on published or unpublished data in terms of sex-dependent differences in midazolam (MDZ) disposition in humans.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.
Hu
Zhe-Yi
ZY
Shanghai Institute of Materia Medica and Graduate School, Chinese Academy of Sciences, 555 Zuchongzhi Rd., Shanghai 201203, PR China. huzheyi_99@hotmail.com
Zhao
Yuan-Sheng
YS
D000284:Administration, Oral; D019540:Area Under Curve; D001682:Biological Availability; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000502:physiology; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008874:Midazolam / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D012727:Sex Characteristics
C040081:1-hydroxymethylmidazolam; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D008874:Midazolam