Triamterene is extensively metabolized by the liver and undergoes important presystemic elimination in normal subjects after oral doses. We examined
triamterene disposition in eight healthy controls and seven patients with
cirrhosis and
ascites. A specific and sensitive HPLC assay was used to measure concentrations of
triamterene and of its major metabolite p-hydroxy-
triamterene sulfate (
OH-T-S). Apparent oral clearance of
triamterene in controls averaged 1617 +/- 219 ml/min. Plasma concentration of
OH-T-S was 7.2 +/- 1.1 times that of the parent compound (estimated by the ratio AUCOH -T-S/ AUCtriamterene ). Urinary recovery of
OH-T-S accounted for 45% of the
triamterene dose. There was 92% reduction in apparent oral clearance of
triamterene (134 +/- 42 ml/min) in patients with
cirrhosis. The ratio AUCOH -T-S/ AUCtriamterene fell to 0.55 +/- 0.2, and urinary recovery of
OH-T-S accounted for only 15% of the dose. These changes in
triamterene kinetics in patients with
cirrhosis resulted in prolongation of its
natriuretic effect, which lasted for up to 48 hr, whereas it was only 8 hr in the controls. These observations reinforce the concept that
cirrhosis is associated with a markedly impaired disposition of drugs that have a large first-pass effect.