Pharmacokinetics of triamterene and its metabolite in man

The pharmacokinetic profiles of triamterene and hydroxytriamterene sulfuric acid ester, the major metabolite of triamterene, were studied in six normal male volunteers using a newly developed specific HPLC analytical method. Following a 100 mg oral dose of triamterene, the plasma concentration time course of the sulfate conjugate parallels that of triamterene in all subjects, but concentrations of the metabolite were more than 10 times higher than unchanged triamterene concentrations at identical sampling times. Interestingly, the renal clearance of the sulfate conjugate was less than that of triamterene. These characteristic features of triamterene disposition were fitted to a compartment model incorporating a first-pass metabolic process. Unbound fractions of triamterene and metabolite in plasma were 0.39 and 0.10 (mean of 6 subjects), respectively. The low unbound fraction of the metabolite in plasma most probably accounts for the low renal clearance of the sulfate conjugate as compared with triamterene.