THE EFFECT OF TENIDAP SODIUM ON THE DISPOSITION AND PLASMA-PROTEIN BINDING OF PHENYTOIN IN HEALTHY MALE-VOLUNTEERS

1 The effects of tenidap sodium 120 mg day(-1) at steady state and placebo on the plasma protein binding and pharmacokinetics of phenytoin were compared in this randomised, double-blind, placebo-controlled, parallel-group study, involving 12 healthy young men, conducted over 34 days. 2 Single oral doses of phenytoin 200 mg were given on days 1-3 and 29-31, and intravenous phenytoin, 250 mg infused over 20 min, was given on days 4 and 32. Tenidap (120 mg day(-1)), or matching placebo, was administered as single oral daily doses from days 8 to 34 inclusive. 3 The plasma protein binding of phenytoin was determined immediately before oral phenytoin administration on days 1 and 29. Pharmacokinetic parameters were estimated from the serum phenytoin concentration-time curves derived on days 4 and 32 following the phenytoin infusions. The differences between the pre- and posttreatment mean percentage of unbound plasma phenytoin and mean pharmacokinetic parameters were compared between treatment groups. 4 Tenidap sodium 120 mg day(-1), at steady state, increased the percentage of unbound phenytoin in plasma by approximately 25%, but did not significantly affect AUC(0,48h) or C-max. 5 Since tenidap increases the percentage of unbound phenytoin in plasma, when monitoring phenytoin plasma concentrations free concentrations of phenytoin should be considered. 6 Tenidap was well tolerated throughout the study.