Pharmacokinetics of glipizide in man: Influence of renal insufficiency

Abstract

Four subjects received 5 mg laC-glipizide orally and 3 subjects 1 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 CI-t2C12 and chromatography showed that in plasma 85% of the total radioactivity corresponded to unchanged glipizide, but in urine 98o/o to more polar and more readily excreted metabolites. The urinary excretion is 68% of t}le dose. The hypoglyeaemie effect of glipizide is comparable to glibenelamide. The administration of 14C-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 norreals, but that the "halflife" of the metabolites was increased to 20 h and more.

Glycemic Control and Hypoglycemia in Veterans Health Administration Patients Converted from Glyburide to Glipizide

“…2,6 In contrast, glipizide is metabolized to inactive metabolites and is not associated with an increased risk of hypoglycemia due to renal dysfunction (defined as glomerular filtration rate [GFR] less than 30 milliliters per minute [mL per min]). 7 The risk of serious hypoglycemia in the elderly (defined as hospitalization, emergency room [ER] admission, or death associated with blood glucose less than 50 mg per dL) was shown to be nearly 2-fold greater with glyburide than glipizide (median doses 5 mg vs. 10 mg per day, respectively) in a retrospective analysis involving 8,576 person-years of exposure to glyburide or glipzide in Medicaid enrollees aged 65 years or older. 8 The increased risk of hypoglycemia with glyburide was confirmed in a recent meta-analysis comparing glyburide with other sulfonylureas.…”

Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease

“…The administration of 14 C-glipizide to patients with RI showed that the rate of disappearance of the unchanged glipizide was approximately the same as in normal subjects, but that apparent t 1/2 of the hydroxylated metabolites was increased to 20 h and more. Because these metabolites are metabolically inactive, such accumulation of metabolites could not lead to a higher risk of hypoglycemia in T2DM patients with RI 73 . Glipizide (2.5 mg once daily, adjusted based on glycemic control to a 10-mg twice a day maximum dose) was evaluated in patients with T2DM and moderate-to-severe CKD and inadequate glycemic control.…”

“…Since many years, gliclazide is available as a modified release formulation 73 . The long-term efficacy and safety of gliclazide modified release in T2DM patients with mild to moderate RI were confirmed by the results of phase III studies.…”

Oral glucose lowering drugs in type 2 diabetic patients with chronic kidney disease

“…One study in two patients with a GFR of 30ml/min and 10 ml/min showed an increase of the t½ of glipizide metabolites to 20h and more. 19 Although several metabolites accumulate in patients with CKD, they do not seem to cause an increased risk of hypoglycemia. 20 Of the second-generation SUs, glipizide is the preferred agent, since it does not increase the risk of hypoglycemia in patients with CKD.…”