President's address: the College of Physicians of Phildelphia.
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Biomedical subjects
Publications and source records attributed to F C Wood.
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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 micrograms.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.