DISPOSITION OF CARBAMAZEPINE AND PHENYTOIN IN PREGNANCY

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