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Effects of Pregnancy on CYP3A and P-glycoprotein Activities As Measured by Disposition of Midazolam and Digoxin: a University of Washington Specialized Center of Research Study

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Publisher Wiley
Specialty Pharmacology
Date 2008 Feb 22
PMID 18288078
Citations 110
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Abstract

The objectives of the study were to evaluate the effects of pregnancy on CYP3A and P-glycoprotein (P-gp) activities, as measured by disposition of midazolam and digoxin, respectively. Thirteen women received digoxin (0.25 mg p.o.) and midazolam (2 mg p.o.) in random order, separated by 1-2 weeks at 28-32 weeks gestation, and the same order was repeated at 6-10 weeks postpartum. Plasma and urine concentrations were determined by liquid chromatography-mass spectrometry and analyzed by noncompartmental methods. Midazolam CL/F(unbound) (593 +/- 237 l/min vs. 345 +/- 103 l/min; P = 0.007), digoxin CL(Renal, unbound) (272 +/- 45 ml/min vs. 183 +/- 37 ml/min; P < 0.002) and digoxin CL(secretion,) (unbound) (109 +/- 34 ml/min vs. 58 +/- 22 ml/min; P < 0.002) were higher during pregnancy than postpartum. These data are consistent with increased hepatic and/or intestinal CYP3A and renal P-gp activities during pregnancy.

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