Antiepileptic drugs: metabolism in pregnancy

In an open prospective clinical study, plasma clearance of phenytoin, phenobarbitone and carbamazepine was assessed in 14 epileptic patients during and after pregnancy. Plasma clearance showed a marked increase during pregnancy, reached a maximum just before or after delivery, and then decreased to early pregnancy values. The relative plasma concentration of carbamazepine-10,11-epoxide to that of carbamazepine increased similarly during pregnancy. The protein binding of carbamazepine and the epoxide was not influenced by pregnancy. A higher rate of hepatic drug metabolism, due to alteration of the physiological state in pregnancy is suggested as the most reasonable explanation. No change in seizure frequency was seen, probably because of frequent dose adjustments in order to keep plasma levels within the optimum range.