Conjugative clearance of 1-naphthol and disposition of its glucuronide and sulfate conjugates in the isolated perfused rat kidney.
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.
Redegeld
F A
FA
State University of Utrecht, Department of Pharmacology, The Netherlands.
Hofman
G A
GA
Noordhoek
J
J
D000818:Animals; D005965:Glucuronates; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008657:Metabolic Clearance Rate; D009284:Naphthols / Q000493:pharmacokinetics*; D010477:Perfusion; D011485:Protein Binding; D051381:Rats; D013431:Sulfates
D005965:Glucuronates; D009284:Naphthols; D013431:Sulfates; C029350:1-naphthol