Conjugative clearance of 1-naphthol and disposition of its glucuronide and sulfate conjugates in the isolated perfused rat kidney

Abstract

Extensive extrahepatic metabolism of 1-naphthol (1-N) was shown to occur in the rat in vivo (clearance = 377 ml/min/kg). The renal contribution to the metabolism of 1-N was investigated in the isolated perfused rat kidney (IPK). 1-N was metabolized to its sulfate (1-NS) and glucuronide (1-NG) conjugate by the IPK. The renal clearance of 1-N ranged from 5.36 to 6.24 ml/min/kidney and was 80 to 95% of the p-aminohippuric acid clearance by the IPK. This indicated that the renal extraction ratio of 1-N was 0.80 to 0.95, showing an important contribution of renal metabolic clearance to the total clearance. Nonlinear kinetics, due to saturation of the metabolic pathways, was shown at 1-N concentrations higher than 10 microM. 1-NS and 1-NG are both secreted in the urine and perfusate, although the urinary excretion of 1-NS is very small whereas the excretion of 1-NG into the urine is extensive, due to differences in the active secretion and protein binding of both conjugates.