The effect of vigabatrin on the pharmacokinetic profiles of orally coadministered doses of phenytoin (PT) and carbamazepine (CBZ) was examined in the rat. Plasma PT and CBZ levels were serially monitored over a 24 h period using an HPLC technique. Coadministration of vigabatrin markedly delayed drug absorption (i.e., longer T max) and significantly reduced the plasma levels of PT and CBZ as assessed by the depression in the respective AUCs. These corresponded to a reduction of 21 and 17%, respectively. The effect on plasma drug concentration was not paralleled by any significant change in the elimination half-lives (t 1 2 ) of the drugs. The similarity in the pattern and magnitude of interaction observed with both drugs suggests a common underlying mechanism. In the absence of hepatic factors, and with vigabatrin's negligible influence on plasma protein binding, gastrokinetic property for vigabatrin is proposed as a likely mechanism to account for the interactions, but clearly further studies are needed to firmly establish this drug action.
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