Pharmacokinetics of glipizide in man: Influence of renal insufficiency

Four subjects received 5 mg14C-glipizide orally and3 subjects1 mg intravenously. The average absorption of the oral dose was nearly 100% with peak plasma levels occurring between 90 and 360 min. The apparent half-life of plasma radioactivity was approximatively 3.7 h, the disappearance of radioactivity following complex kinetics due to metabolism of the drug. Extraction with CH2Cl2 and chromatography showed that in plasma 85% of the total radioactivity corresponded to unchanged glipizide, but in urine 98% to more polar and more readily excreted metabolites. The urinary excretion is 68% of the dose. The hypoglycaemic effect of glipizide is comparable to glibenclamide. The administration of14C-glipizide to two patients with renal insufficiency showed that the metabolism of the drug is independent of kidney function, that the rate of disappearance of the unchanged glipizide was approximately the same as in normals, but that the “halflife” of the metabolites was increased to 20 h and more.