Glipizide pharmacokinetics and response in diabetics

The pharmacokinetics of and response to glipizide were studied in six insulin-independent diabetics by radioimmunoassay for glipizide and insulin. Blood glucose was also monitored. Beside control (off glipizide) the patients were studied when given 10 mg glipizide either as a single daily dose or divided into two doses. The peak drug concentration was reached on an average within 1.8-2.3 h. The AUCs did not differ between the two dosage regimens. The mean elimination half-life was 4.7 +/- 0.4 h, Vd 17.0 +/- 2.6 l, and the calculated total clearance 41.6 +/- 4.3 ml/min (mean +/- s.e.m.). In one patient a more than two-compartment pharmacokinetic model was obvious. The once or twice daily dosage regimens did not differ significantly in their ability to reduce blood glucose, but the overall efficacy of the therapy was poor in these patients. The maximal efficacy of a single 10-mg dose of glipizide to reduce blood glucose was maintained at the same level between 1.5 and 8 h despite the continued rapid falling of serum glipizide concentration over this period.