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 early to late pregnancy and after delivery. Methods: Twelve women were studied on three occasions during pregnancy (early, 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-containing 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 estimated 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 < .0001) and NAT2 (P < .01). The mean metabolic ratios for CYP1A2 during pregnancy (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 significantly lower than after delivery (0.66). There was no significant difference 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.