The effect of pregnancy on cytochrome P4501A2, xanthine oxidase, and N-acetyltransferase activities in humans

Objective: Our objective was to evaluate the activity of cytochrome P4501A2 (CYP1A2), xanthine oxidase (XO), and X-acetyltransferase 2 (NAT2) from ear ly to late pregnancy and after delivery. Methods: Twelve women were studied on three occasions during pregnancy (ear ly, 8-16 weeks' gestation; middle, 20-28 weeks' gestation; and late, 32-39 weeks' gestation) and about 1 month after delivery. Caffeine was used as a metabolic probe. After the women ingested a can or a bottle of caffeine-con taining soft drink, urine samples were collected for 12 hours. The caffeine metabolites measured were 5-acetyl-amino-6-amino-3-methyluracil (AAMU), 1- methylxanthine (IX), 1-methyl-uric acid (1U), 1,7-dimethyl-uric acid (17U), and 1,7-dimethylxanthine (17X). The hepatic enzyme activities were estimat ed by the urinary caffeine metabolic ratios as follows: CYP1A2 = (AAMU + 1X + IU)/17U; XO = 1U/(IX + 1U); NAT2 = AAMU/(AAMU + IX + 1U). Results: Statistically significant differences were found in CYP1A2 (P < .0 001) and NAT2 (P < .01). The mean metabolic ratios for CYP1A2 during pregna ncy (6.80, 5.18, and 4.97 for the early phase, middle phase, and late phase , respectively) were significantly lower than the ratio after delivery (10. 39). The mean metabolic ratio for NAT2 in the early phase (0.57) was signif icantly lower than after delivery (0.66). There was no significant differen ce in metabolic ratios for XO during pregnancy and after delivery. Conclusion: The data demonstrate that pregnancy influences CYP1A2 and NAT2 activity. CYP1A2 activity decreases not only in late pregnancy but also in early and middle pregnancy.