Biliary excretion of chlorthalidone in humans

A single oral dose of the diuretic chlorthalidone (100 or 200 mg) was given to six cholecystectomized patients with T-tube drainage of the common bile duct, and the 24 h bile and urine were collected during 3--7 days. Urinary recovery of chlorthalidone was 23--27 per cent of the dose, which is in the range of that in healthy volunteers. Chlorthalidone concentration in bile was 11--44 times lower than urine concentration in corresponding periods, and biliary recovery was only 0.6--1.4 per cent of the dose. When compared from equal periods of sampling of bile and urine, the same relative amount of drug was found in bile, whether the 100 or 200 mg dose had been given (viz., a fraction of 2.5--4.7 per cent and 2.5--5.7 per cent of corresponding urinary amounts respectively). It was concluded that excretion into bile constitutes only a minor route of elimination for unchanged chlorthalidone. Bile samples treated with glucuronidase and sulphatase showed no increase of chlorthalidone concentration. The open acid analogue of chlorthalidone, 3-(4-chloro-3-sulphamoylbenzoyl)-benzoic acid, was apparently not formed as a human metabolite, as evidenced by gas chromatographic analysis of both urine and bile.