The presence of a microsomal UDP‐glucuronyl transferase for bilirubin in homozygous jaundiced gunn rats and in the crigler‐najjar syndrome

Gerard B. Odell, Julio O. Cukier, Glenn R. Gourley – 1 July 1981 – The infusion of a closely related derivative of bilirubin, its dimethyl diester (DME), into jaundiced (jj) Gunn rats was associated with biliary excretion of mono‐and diglucuronides of bilirubin. In vitro incubation of DME with liver microsomes from jj rats demonstrated sequential demethylation and glucuronidation of DME. Liver microsomes from a patient with the Crigler‐Najjar syndrome were unable to form glucuronides of bilirubin in vitro unless DME was used as substrate.

The effects of variation in dietary protein and ethanol on hepatic microsomal drug metabolism in the rat

Mack C. Mitchell, Esteban Mezey, Willis C. Maddrey – 1 July 1981 – The effects of chronic ethanol consumption and variations in dietary protein content on microsomal drug metabolism were studied in rats pair‐fed liquid diets containing 10, 20, or 30% dietary protein with or without ethanol. In vivo drug metabolism was measured by aminopyrine breath tests and aminopyrine blood elimination kinetics. In vitro drug metabolism was assessed by measuring aminopyrine N‐demethylase activity in the hepatic microsomal fraction.

Plasma clearance of intravenous chenodeoxycholic acid in rabbits with varying severity of hepatocellular necrosis

Malcolm Mackinnon, Pauline Hall – 1 July 1981 – The plasma clearance of an i.v. bolus of chenodeoxycholic acid (10 μm per kg) was determined in rabbits with graded degrees of hepatocellular necrosis produced by i.p. injection of carbon tetrachloride. Plasma chenodeoxycholic acid levels were determined by radioimmunoassay, and the volume fraction of necrosis was quantitated by a computerized (Quantimet 720) system. Impaired plasma clearance was observed only when necrosis was extensive, and the volume fraction of necrosis >34%.

Hepatic and extrahepatic glucuronidation of lorazepam in the dog

John F. Gerkens, Paul V. Desmond, Steven Schenker, Robert A. Branch – 1 July 1981 – The pharmacokinetic disposition of lorazepam was investigated in sham‐operated anesthetized dogs, dogs with hepatic devascularization, and dogs with total splanchnic devascularization following i.v. administration of 0.3 mg per kg of the drug. In sham‐operated dogs, lorazepam distribution was extensive (100 ± 15.2 liters) and clearance approximated expected liver blood flow (971 ± 91 ml per min). Lorazepam glucuronide levels in plasma rose rapidly in the first hour and reached a plateau by 5 hr.

Muscle protein breakdown in liver cirrhosis and the role of altered carbohydrate metabolism

Giulio Marchesini, Marco Zoli, Angela Angiolini, Cristina Dondi, Francesco B. Bianchi, Emilio Pisi – 1 July 1981 – The rates of muscle protein breakdown, as estimated by the urinary excretion of 3‐methylhistidine, were assessed in 30 cirrhotics and 15 controls on a strictly controlled diet. 3‐Methylhistidine excretion was increased in cirrhotics irrespective of the etiology of the disease, and correlated with basal glucagon levels and with the insulin/glucagon ratio.

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