1. The apparent renal clearance of intravenously injected [14C]
glycocholate and [3H]
chenodeoxycholate-3-sulphate was estimated in 22 patients with
cholestasis. The degree of protein binding of the
isotopes in serum from these patients was determined. The effects of pharmacological agents, changes in urine flow rate and pH on renal clearance was studied. 2. The mean renal clearance of [14C]
glycocholate was 1 . 7 +/- 0 . 4 ml/min (mean +/- SEM), and that of [3H]
chenodeoxycholate-3-sulphate was 6 . 4 +/- 0 . 9 ml/min. [14C]
Glycocholate was 80 . 1%
protein bound and [3H]
chenodeoxycholate-3-sulphate 96 . 5%
protein bound. 3. Comparisons of the observed clearance rates with those calculated on the basis of glomerular filtration of the unbound fraction suggest that whereas [14C]
glycocholate is predominantly reabsorbed by the renal tubules, [3H]
chenodeoxycholate-3-sulphate appears in the urine mainly as the result of tubular secretion. 4.
Probenecid,
ethacrynic acid,
frusemide and
bendrofluazide decreased the clearance of both
bile acids, implying competition for secretion via the proximal tubular organic
acid secretory pathway between these compounds and
bile acids. 5. Passive non-ionic diffusion does not seem to be an important mechanism in the renal excretion of
bile acids as changes in urine flow rate and pH did not influence
bile acid clearance. 6. A greater affinity of the proximal tubular organic
acid secretory pathway for sulphated than for non-sulphated
bile acids may explain the higher observed renal clearance rate of sulphated
bile acids.