Carbamazepine‐induced acceleration of diphenylhydantoin and warfarin metabolism in man

Abstract

Diphenylhydantoin half-life was determined in 5 patients before and during treatment with carbamazepine. It caused a significant decrease in the diphenylhydantoin half-life from 10.6 hours to 6.4 hours. Seven patients who for a period had been given diphenylhydantoin were also started on carbamazepine. This resulted in a fall in serum diphenylhydantoin levels in 3 of the patients. Alterations in warfarin half-life, serum warfarin, and plasma prothrombinproconvertin concentration during carbamazepine treatment were compatible with a stimulation of warfarin metabolism. The effect of carbamazepine on diphenylhydantoin and warfarin metabolism is probably explained by an induction of the drug-metabolizing enzyme system in the liver.

Carbamazepine-Phenprocoumon Interaction

“…C Y P 3 A 4 [1], Furthermore C B Z effects on biotransforma tion o f a number o f other drugs led to the hypothesis that C B Z in addition has an influence on various isoenzymes o f the cytochrome P 450 complex, e.g. C Y P 2 C 9 and C Y P 2 C 1 9 [1], In this line are some previous reports, which demonstrated decreases o f warfarin half-life in serum under concomitant administration o f C B Z [2][3][4][5].…”

Effects of Various Antiepileptic Drugs on Plasma Levels of Lamotrigine, a Novel Antiepileptic, in Rats

“…CBZ has been re ported to increase liver microsomal enzymes responsible for drug metabolism, resulting in a decreased plasma level of a concomitantly administered drug [10]. Furthermore, Konishi et al [11] [16] reported the hepatic competition between VPA and LTG forglucuronidation in humans.…”

A simple method for the administration of doxapram.

“…Significantly, the lowest concentrations noted (Figure 1) were found in a patient receiving carbamazepine, a drug known to induce microsomal enzyme activity (Hansen et al, 1971). In this subject, plasma doxapram concentrations fell with a half-life of 155 min.…”