Studies on monocomponent insulin. V. pharmacokinetics of soluble insulin preparations using in situ animal model

Pharmacokinetics of soluble monocomponent insulin preparation was examined by using an in situ experimental model of rabbits. Rabbits were laparotomized under anesthesia, and prepancreatic duodenal vein, splenic vein, and hepatic artery were ligated, and cannulae were inserted into the hepatic vein, portal vein, abdominal aorta, and renal vein. After administration of the monocomponent insulin preparation, blood was drawn periodically from each cannula, exogenous insulin level was measured, and kinetic parameters were calculated from the blood level curves from the arteries. The parameters obtained were disappearance rate constant (Kel) of 0.128 plus or minus 0.013 hr-1 and biological half-life (T1/2) of 5.50 plus or minus 0.49 min. Rate of insulin uptake by each organ was calculated from the difference in arterial and venous blood levels at each time period and values were 12% for the lever and 31% for the kidney. No definite uptake was found in the digestive tract. Relationship between the potency of insulin and blood levels suggested that the minimum effective blood level of this insulin preparation was 20 - 30 microU/ml.