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- Title
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.
- Authors
Hebert, MF; Easterling, TR; Kirby, B; Carr, DB; Buchanan, ML; Rutherford, T; Thummel, KE; Fishbein, DP; Unadkat, JD
- 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/Funbound (593 ± 237 l/min vs. 345 ± 103 l/min; P = 0.007), digoxin CLRenal, unbound (272 ± 45 ml/min vs. 183 ± 37 ml/min; P < 0.002) and digoxin CLsecretion,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.Clinical Pharmacology & Therapeutics (2008); 84, 2, 248–253 doi:10.1038/clpt.2008.1
- Subjects
P-glycoprotein; MIDAZOLAM; DIGOXIN; PREGNANCY; PREGNANT women
- Publication
Clinical Pharmacology & Therapeutics, 2008, Vol 84, Issue 2, p248
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1038/clpt.2008.1