Pharmacokinetics and pharmacodynamics of glipizide in healthy volunteers

Int J Clin Pharmacol Ther Toxicol. 1983 Feb;21(2):98-107.


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.

MeSH terms

  • Administration, Oral
  • Adult
  • Biological Availability
  • Blood Glucose / metabolism
  • Female
  • Glipizide / metabolism
  • Glipizide / pharmacology*
  • Glucagon / metabolism
  • Humans
  • Injections, Intravenous
  • Insulin / blood
  • Kinetics
  • Male
  • Middle Aged
  • Sulfonylurea Compounds / pharmacology*
  • Time Factors


  • Blood Glucose
  • Insulin
  • Sulfonylurea Compounds
  • Glucagon
  • Glipizide