Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A activity) during pregnancy

Objective: The purpose of this study was to determine whether drug metabolism (CYP1A2, CYP2D6 and CYP3A) activity varies in the pregnant state compared with the nonpregnant state. Study design: Subjects were studied at 14 to 18 weeks of gestation, 24 to 28 weeks of gestation, and 36 to 40 weeks of gestation and again at 6 to 8 weeks after the delivery. Twenty-five subjects completed all 4 study periods and had evaluable data. Salivary caffeine clearance was used as a measure of CYP1A2 activity; dextromethorphan O- and N-demethylation were used to assess CYP2D6 and CNP3A activity, respectively. Results: CYP1A2 activity was significantly reduced at all periods of the pregnancy as compared with the postpartum period during the first (-32.8% +/- 22.8%), second (-48.1% +/- 27%), and third periods (-65.2% +/- 15.3%), respectively. In contrast, CYP2D6 activity was increased significantly throughout the pregnancy (25.6% +/- 58.3% at 14-18 weeks of gestation, 34.8% 41.4% at 24-28 weeks of gestation, and 47.8% +/- 24.7% at 36-40 weeks of gestation) as compared with the postpartum period. CYP3A activity was consistently, significantly increased (35%-38%) during all stages of the pregnancy. Conclusion: Opposing changes in drug metabolism occur during pregnancy, with CYP1A2 activity decreased and CYP2136 and CYP3A activities increased. The direction of dosing adjustments during pregnancy will depend on the drug and the enzyme that is responsible for its metabolism. (C) 2005 Elsevier Inc. All rights reserved.