Pharmacokinetics and biliary excretion of bromosulphophthalein, [³H]‐ouabain and [³H]‐taurocholic acid in rats with glycerol‐induced acute renal failure

Abstract

1 The pharmacokinetics and biliary excretion of bromosulphophthalein (BSP), ouabain and taurocholic acid (TChA) have been studied in rats with glycerol-induced acute renal failure (ARF). 2 In rats with ARF, the hepatic uptake and initial biliary excretion of BSP were decreased. In addition, the rate of BSP conjugation with glutathione by rat liver homogenates was also decreased. This latter change may contribute to the initial decrease in the biliary excretion of BSP. 3 No change was found in the hepatic uptake and biliary excretion of ouabain, but the area under the concentration-time curve was increased and the plasma clearance (Clp) decreased in rats with ARF. This decrease in Clp was not due to reduced renal excretion. 4 The decreased Clp of ouabain in rats with ARF may come from reduced tissue binding and a concomitant decrease in its volume of distribution (Vd). 5The hepatic handling of TChA appeared unaltered in ARF, but the rate constant for the terminal part of the concentration-time curve (f) was decreased. This change probably resulted from a large increase in Vd in rats with ARF. 6 It is concluded that the decreased uptake of BSP was not due to a non-specific disturbance of hepatocyte function in ARF because the hepatic handling of ouabain and TChA were unaltered.

Effects of Uremic Toxins on Hepatic Uptake and Metabolism of Erythromycin

“…Studies showed that the hepatic uptake and initial biliary excretion of bromosulfophthalein were decreased in rats with glycerol-induced acute renal failure (Bowmer and Yates, 1984). A similar phenomenon was observed for another organic anion, indocyanine green (Yates et al, 1983).…”

“…The effects of renal failure on hepatic uptake of organic anions were documented in early studies (Yates et al, 1983;Bowmer and Yates, 1984). Studies showed that the hepatic uptake and initial biliary excretion of bromosulfophthalein were decreased in rats with glycerol-induced acute renal failure (Bowmer and Yates, 1984).…”

Effects of chronic kidney disease and uremia on hepatic drug metabolism and transport

“…There is increasing awareness that uptake transport of drugs across the sinusoidal membrane of hepatocytes regulates the access of drug substrates to hepatocelluar enzymes as well as canalcular transport into the bile canaliculi, and can be a rate-limiting step in the overall process of hepatic drug clearance. 46 In 1984, Bowmer, Yates and their colleagues 47 , 48 47 , 48 reported that the hepatic uptake of two anionic dyes (indocyanin green and bromosulfophthalein) that are non-selective OATP substrates were reduced in acute renal failure rats. The functional and clinical significance of these findings did not become evident until a series of recent investigations showed that inhibition of uptake transport into the liver may explain to a large extent the reduced non-renal clearance observed in CKD patients for several commonly used drugs that are moderately good to high affinity substrates of human hepatic OATPs: erythromycin, 9 , 49 eprosartan, 50 fexofenadine, 8 and digoxin.…”

Hepatic arterial perfusion decreases intrahepatic shunting and maintains glucose uptake in the rat liver

“…BSP was measured according to established techniques by measuring its absorption in a spectrophotometer (Cecil 2020, ultraviolet/ visible light spectrophotometer) at 570 nm [10]. The colour of BSP may degrade upon exposure to air and, in order to minimise this, a glycine-NaOH buffer pH=10.0 was added to each sample.…”