The effect of valproate and diazepam on toxicokinetic of verapamil

A Hamdi1, M Lahouel2, H Rechak3. 1USTHB University, Algiers,Dar El Beida, Algeria, 2Jijel University, Jijel,Jijel, Algeria, 3Jijel University, Jijel,Jijel, Algeria

Polymedication is a frequent problem ,in particular for the elder people .The major risque is related to toxicokinetic interactions.Verapamil ,an inhibitor of calcium channels , is prone to this type of interactions whene it is taken in combination with valproate or with diazepam.

This study investigates the effect of valproate and diazepam on the toxicokinetic of verapamil in rats after oral (10 mg/kg) and intravenous (1 mg/kg) administration of verapamil in the presence or absence of valproate and/or diazepam .Valproate and diazepam altered verapamil pharmacokinetics compared to verapamil alone .The presence of valproate and diazepam significantly (p<0.05) increased the bioavaibility of verapamil and decreased its total plasma clearance (CL) . Valproate and diazepam enhance the oral and intravenous bioavailability of verapamil throught displacement from protein binding sites .valproate may also enhance the bioavailability of verapamil by inhibiting the CYP2C9-mediated metabolisme and UGT inhibition .Therefore ,concurrent use of verapamil and valproate/diazepam should be monitored closely to potential drug interactions for safe therapy of cardiovascular diseases.

Key words: verapamil ,valproate ,diazepam ,toxicokinetics ,drug-dryg interactions, CYP 450.

Table 1. Mean pharmacokinetic parameters of verapamil in rat plasma.

Table 2. Mean pharmacokinetic parameters of verapamil in ratplasma.