Pharmacokinetics of midaglizole, a new hypoglycaemic agent, in healthy subjects

The objective of this study was to evaluate the pharmacokinetics of midaglizole, a new orally effective hypoglycaemic agent, in healthy male subjects. In Study I, volunteers were given single oral doses of 150, 200, 300, and 500 mg of midaglizole 20 min before breakfast. In Study II, 200 mg of midaglizole was given 30 min after breakfast. In Study III, multiple oral administration study was carried out at a dose of 200 mg t.i.d. 20 min before meals for 7 days. The disposition of midaglizole was adequately described by a one-compartment open model with first order absorption. It was essentially dose-dependent up to 500 mg given orally. The pharmacokinetic parameters calculated by employing this model indicated that the disposition of this drug was characterized by good absorption from the intestine, a wide distribution in the body, and a rapid excretion via the kidneys. The absorption rate of midaglizole from the intestine was definitely slowed by the presence of food, probably due to a decrease in the rate of gastric emptying. No clinical significant accumulation of midaglizole in the body was observed during or after multiple doses. A linear correlation was found between the area under the curve of plasma concentration of midaglizole versus time and the area calculated from the curve of change in blood glucose level versus time after oral administration of midaglizole.