ESTIMATION OF INDIVIDUAL ACTION PROFILES OF THERAPEUTICALLY ADMINISTERED INSULIN BASED ON BLOOD-GLUCOSE LEVELS IN DIABETIC DOGS AND PATIENTS

To acquire detailed insight into the pharmacokinetics and pharmacodyna mics of insulin, a computer-aided procedure was established. Employing an individually identifiable state model of insulin and glucose metab olism, the metabolic situation of diabetic patients is characterized. Pharmacokinetics of insulin and its effect on glucose metabolism are a ssessed using deconvolution techniques under the influence of specifie d experimental conditions. The entire procedure was validated in chron ically diabetic dogs following injections by intravenous, subcutaneous , and peritoneal routes. The practical applicability of the approach w as verified in a selected group of C-peptide negative, type I diabetic patients. Following subcutaneous injection, a test dose of 200 mU/kg (dogs) or 100 mU/kg (patients) is fully recovered by the model-based e stimates, but only between 70 and 80% of the dose appears as an effect ive insulin-glucose interaction when intravenous or peritoneal routes are used. The calculated profiles of glycaemia-effective insulin provi de the basis for computer-aided prediction of the outcome of therapeut ic regimes in terms of daily profiles of glycaemia and insulinaemia. T he results demonstrate the feasibility of model-based estimation of in sulin effects. Having provided appropriate model parameters, the blood glucose levels measured in response to insulin administration are the only experimental data required.