Pharmacokinetics and pharmacodynamics of glipizide in healthy volunteers.
Single doses of 14C-glipizide were given intravenously (1 mg/4.7 microCi) and orally (5 mg/8.0 microCi) to six healthy volunteers in a crossover study to investigate both pharmacokinetics and effects of glipizide. Based on recoveries of total 14C in urine the gastrointestinal absorption of glipizide was complete. The extent of first-pass metabolism averaged 4.8 +/- 0.04% (SE) of the dose. The pharmacokinetics of i.v. glipizide could be described by a two-compartment open model. The volume of the central compartment was 4.25 +/- 0.25 l and the steady-state volume of distribution averaged 11.7 +/- 1.1 l. Glipizide concentrations in red cells and saliva were only 4% and 1%, respectively, of the concentrations in plasma. The half-life of glipizide elimination averaged 3.3 h both after i.v. and p.o. administration. The total plasma clearance of glipizide was 42.2 +/- 5.4 ml/min, whereas that of protein unbound fraction was 1350 +/- 130 ml/min. Renal clearance was dependent on urinary pH, but on the average it contributed to the total clearance only by 5%. About 17% of the i.v. dose was found in the feces. Intravenous glipizide caused a rapid increase (peak at 6 min, about four-fold) in plasma insulin lasting for 30 min. Plasma glucagon showed an almost simultaneous decrease. These responses were followed by a more sustained decrease in plasma glucose. After oral administration of glipizide the maximal effects on plasma insulin and glucose were seen before the peak concentrations of glipizide in plasma.
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D005913:Glipizide / Q000378:metabolism / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D013453:Sulfonylurea Compounds; D005934:Glucagon; D005913:Glipizide