Pharmacokinetics and Pharmacodynamics of Glipizide After Once‐Daily and Divided Doses

Abstract

Study Objective. To determine the pharmacokinetics and pharmacodynamics of glipizide given as a single, oral, 20‐mg dose, versus three different divided‐dose regimens totaling 20 mg each.Design. Randomized (in order of dosing regimens), open‐label, crossover study.Setting. University medical center clinical research center.Patients. Six subjects with noninsulin‐dependent diabetes mellitus.Interventions. Patients were studied on four separate occasions separated by at least 3 days. The divided‐dose regimens were designed to simulate delayed absorption of the drug over 2, 4, and 8 hours. Blood samples for measuring glipizide, glucose, and C‐peptide were obtained over 24 hours.Measurements and Main Results. Glipizide peak concentrations and time to peak differed significantly with the dosage schedule; when smaller doses were administered more often, peak concentrations were lower and more delayed. The mean values for area under the curve from time zero to infinity (range 7240.7–10,001.8 μg·L‐1·hr−1; 16,226‐22,414 nmol·L−1·hr−1), clearance (0.44‐0.64 ml·min−1·kg−1; 0.07‐0.11 ml·sec−1·kg−1), post‐distribution phase volume (0.17‐0.25 L·kg−1), and half‐life (4.2–5.4 hrs) were not significantly different among regimens. Neither morning fasting glucose nor maximum and minimum times and concentrations of glucose and C‐peptide over 24 hours were statistically different among regimens. Similarly, no significant differences were found in area under the concentration‐time curve for glucose and C‐peptide measured over 2.5 hours after each meal and from time zero to 24 hours.Conclusions. The timing of a glipizide dose in relation to a meal and simulated delayed or prolonged absorption appear to have little influence on the drug's pharmacodynamic effects.