Disposition of carbamazepine and phenytoin in pregnancy

Free and total plasma concentrations of phenytoin (PHT) and carbamazepine (CBZ) and its active metabolite carbamazepine-10, 11-epoxide (CBZ-E) were determined in a prospective study of 86 pregnant epileptic women. The pharmacokinetics of PHT and CBZ during the three trimesters were compared with kinetics at least 10 weeks postpartum. Plasma clearance and unbound CBZ clearance were slightly decreased during the last trimester. Total and free plasma CBZ-E concentrations did not change significantly during pregnancy. Plasma PHT clearance, on the other hand, increased from the first trimester. A less pronounced increase was observed for clearance of unbound PHT; the increase was statistically significant only during the third trimester.