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.
Clin Pharmacol Ther
; 84(2): 248-53, 2008 Aug.
Article
en En
| MEDLINE
| ID: mdl-18288078
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Midazolam
/
Embarazo
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP
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Periodo Posparto
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Digoxina
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Citocromo P-450 CYP3A
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adult
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Female
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Humans
Idioma:
En
Revista:
Clin Pharmacol Ther
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos