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• W2013119377 endingPage "538" @default.
• W2013119377 startingPage "531" @default.
• W2013119377 abstract "Studies examining sex differences in CYP3A activity have produced conflicting results. Our objective is to investigate whether sex differences exist in CYP3A activity as assessed by intravenous (IV) or oral midazolam pharmacokinetic analysis in healthy volunteers.Data from 13 previous studies were used. A single dose of IV midazolam (0.025 mg/kg) was administered to 66 white adults (37 women and 29 men; mean age, 36.3+/-7.7 years). A single dose of oral midazolam, 0.075 mg/kg (5 studies), 0.15 mg/kg (1 study), or 5 mg (1 study), was administered to 72 adults (71 white and 1 Asian; 37 women and 35 men; mean age, 38.3+/-8.9 years). Pharmacokinetic parameters were determined via population methods by use of a nonparametric adaptive grid program and a 2-compartment IV and 1-compartment oral absorption model. The maximum a posteriori probability Bayesian method was used to estimate each subject's pharmacokinetic parameters. Monte Carlo simulation was performed to determine the probability distribution of the area under the concentration-time curves (AUCs).Women exhibited 11% higher mean weight-corrected total body midazolam clearance and 28% higher oral clearance compared with men (P<or=.01). The median AUC of IV midazolam was 0.05 mg.h/L (range, 0.02-0.14 mg.h/L) in women and 0.06 mg.h/L (range, 0.02-0.14 mg.h/L) in men. The median AUC of oral midazolam was 0.11 mg.h/L (range, 0.02-0.60 mg.h/L) in women and 0.12 mg.h/L (range, 0.04-0.45 mg.h/L) in men.Although women showed significantly greater hepatic and intestinal CYP3A activity, only a minor sex difference in AUC was noted. Therefore the observed disparity may be of negligible clinical importance." @default.
• W2013119377 created "2016-06-24" @default.
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• W2013119377 date "2006-11-01" @default.
• W2013119377 modified "2023-10-14" @default.
• W2013119377 title "Sex differences in CYP3A activity using intravenous and oral midazolam" @default.
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• W2013119377 doi "https://doi.org/10.1016/j.clpt.2006.08.014" @default.
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