To clarify renal handling of
rhodamine 123, a substrate for
P-glycoprotein, in normal and diseased states, in-vivo clearance studies were performed with normal rats and rats with
glycerol-induced
acute renal failure. For normal rats the excretion ratio of unbound
rhodamine 123-to-inulin was 3.25, indicating the presence of the renal tubular secretion of
rhodamine 123. Co-administration of
cyclosporin, a P-glycoprotein inhibitor, significantly reduced tubular secretion of
rhodamine 123. Administration of
glycerol induced both an increase in blood
urea nitrogen and a reduction in the glomerular filtration rate, confirming the induction of
acute renal failure. Total plasma, renal, and tubular secretory clearances of
rhodamine 123 were significantly lower for rats with
acute renal failure than for control rats. There was no difference between the
ATP content of the renal cortex in control rats and those with
acute renal failure. In addition to the decrease in renal clearance, a decrease in the biliary clearance of
rhodamine 123 was also observed in rats with
acute renal failure. These results imply that
rhodamine 123 is secreted via
P-glycoprotein in renal tubules and that the renal secretory clearance of
rhodamine 123 was reduced after
acute renal failure, probably because of impairment of
P-glycoprotein.