PHARMACOKINETICS OF MIGLITOL - ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION FOLLOWING ADMINISTRATION TO RATS, DOGS, AND MAN

The absorption, distribution, metabolism, and excretion of miglitol ox yethyl)-2-(hydroxymethyl)-3,4,5-piperidinetriol, CAS 72432-03-2, BAY m 1099) have been studied following single and repeated administration of non-labelled and radiolabelled (H-3, C-14) drug to rats, dogs, and human volunteers via different routes of administration (intravenous, oral, intraduodenal) and at various doses (0.3-450 mg/kg). After intra venous administration, miglitol is excreted rapidly and completely via the renal route. No indication was found for a metabolization of radi olabelled miglitol. The (renal) clearance of miglitol is in the range of the glomerular filtration rate. Miglitol is rapidly eliminated from plasma with apparent elimination half-lives of 0.4-1.8 h. Miglitol is virtually not bound to plasma proteins. After oral administration mig litol is rapidly and at low doses also completely absorbed. At higher doses (greater than or equal to 5 mg/kg in rats and dogs, > 50 mg in h umans) a saturation of absorption becomes evident. Miglitol is distrib uted predominantly in the extracellular space. The volumes of distribu tion are low (0.3-0.8 1/kg). In rats high concentrations were initiall y found in the kidneys, the blood and some well perfused tissues. The permeation across the blood/brain barrier is very low. Elimination fro m organs and tissues occurs rapidly resulting in very low residual rad ioactivity in the body 2 days after dosing (< 0.9 % of the dose). At t his very low concentration level a terminal elimination phase of radio activity characterized by half-lives of 50-110 h was observed giving r ise to a slight tendency for accumulation (accumulation factors < 6) f ollowing repeated administration to rats. In pregnant rats [C-14]migli tol crossed the placental barrier slowly and to a limited extent. In l actating rats miglitol was found in milk in concentrations similar to those in the maternal plasma.