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.


METHODS
Subjects were studied at 14 to18 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 CYP3A 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.


CONCLUSIONS
Opposing changes in drug metabolism occur during pregnancy, with CYP1A2 activity decreased and CYP2D6 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.
Tracy
Timothy S
TS
Department of Experimental and Clinical Pharmacology and Center of Excellence in Women's Health, University of Minnesota, Minneapolis, Minn, USA. tracy017@umn.edu
Venkataramanan
Raman
R
Glover
Douglas D
DD
Caritis
Steve N
SN
D000293:Adolescent; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D002110:Caffeine / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003915:Dextromethorphan / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006801:Humans; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism*
D002110:Caffeine; D003915:Dextromethorphan; D001189:Aryl Hydrocarbon Hydroxylases; D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; C054116:norlevorphanol