期刊
CLINICAL PHARMACOLOGY & THERAPEUTICS
卷 84, 期 2, 页码 248-253出版社
WILEY
DOI: 10.1038/clpt.2008.1
关键词
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资金
- NCRR NIH HHS [M01RR-00037, M01 RR000037] Funding Source: Medline
- NICHD NIH HHS [P50HD0444, P50 HD044404] Funding Source: Medline
- NIGMS NIH HHS [GM07550] Funding Source: Medline
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 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.
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