Tenidap sodium does not alter the clearance or plasma protein binding of tolbutamide in healthy male volunteers.

1. This randomised, double-blind, parallel group study in 12 healthy young men compared the effects of tenidap sodium 120 mg day-1, at steady state, with placebo on the plasma protein binding and clearance of tolbutamide. 2. Each subject received a 1000 mg intravenous infusion of tolbutamide given over 5 min on day 1 of the study, and again on day 30 following 22 days of successive tenidap or placebo administration. 3. The percentage of unbound tolbutamide in plasma was determined immediately before each infusion. Mean pharmacokinetic parameters (system plasma clearance, terminal phase rate constant, apparent volume of distribution at steady state) of tolbutamide were derived from individual tolbutamide plasma concentration-time curves generated after infusion. The within group day 30 minus day 1 differences were compared between treatment groups. 4. Tenidap was shown to have no statistically or clinically significant effects on any of the parameters assessed. These results indicate that tenidap does not induce or inhibit the P450IIC9 isozyme which metabolises tolbutamide and that tenidap does not displace tolbutamide from plasma protein binding sites. 5. Both tenidap and tolbutamide were well tolerated. No severe treatment-related adverse events were reported, no subject withdrew from the study, and there were no reports of treatment-related laboratory abnormalities, or significant variations in vital signs.

RCT Entities:   Population Interventions Outcomes