John B. Watkins, Curtis D. Klaassen – 1 July 1981 – Valproic acid (VPA) is an anticonvulsant agent which produced marked choleresis in the rat. Bile flow rate increased from 50 to 60 μl per min per kg to 120 to 145 μl per min per kg immediately after i.v. injection of VPA (37.5 to 150 mg per kg; 2 ml per kg) in male Sprague‐Dawley rats. The duration of maximal bile flow was dose‐dependent and increased from 30 min (37.5 mg VPA per kg) to approximately 2 hr (150 mg VPA per kg). Choleresis diluted the biliary concentrations of bile acids, Cl−, cholesterol, and phospholipids.

Edward L. Krawitt, Richard J. Albertini, Duane D. Webb, Bette F. Chastenay, Greg Holdstock, Bruce R. Macpherson – 1 July 1981 – Studies were undertaken in 32 patients with hepatitis B‐negative or ‐positive chronic active hepatitis or chronic persistent hepatitis to define the relationship between immunoregulatory activity and the HLA‐B8 and B12 phenotypes. Suppressor T‐cell activity measured by a concanavalin A‐induced suppressor system using allogeneic responder cells was dependent on which individual was selected as a source of responder cells.

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.

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.

Charles S. Davidson – 1 July 1981

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%.

1 July 1981

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.

Serge Erlinger – 1 July 1981

Harold O. Conn – 1 July 1981