Endogenous uremic substances are not involved in the reduced hepatic extraction of metoprolol in bilateral ureter-ligated rats.

The hepatic extraction of metoprolol is reduced in rats with bilateral ureter ligation (BUL)-induced renal failure. The aim of the present study was to evaluate the effect of uremic substances on the hepatic metabolism of metoprolol in rats with BUL. The metabolic rate in the liver microsomes of BUL rats was similar to that in sham rats, and there was no significant difference between sham and BUL rats in the effect of the supernatant of liver homogenates on the metabolism.

Mechanism responsible for the decreased hepatic NADPH generation rate in rats with bilateral ureter ligation-induced renal failure.

We previously reported that a decrease in hepatic NADPH generation results in reduced hepatic first-pass clearance of propranolol in rats with bilateral ureteral ligation (BUL)-induced renal failure. The aim of the present study was to evaluate the mechanisms responsible for the reduced NADPH generation in the supernatant of liver homogenates (SUP) obtained from rats with BUL. The NADPH generation in the SUP in the presence of NADP(+) was decreased in BUL rats as compared with control rats.