PHARMACOKINETICS AND EFFECTS OF DIFFERENT FORMULATIONS OF GLIPIZIDE IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Comparisons were made in 24 (study 1) and 10 (study 2) patients with non-insulin-dependent diabetes mellitus (NIDDM) concerning the single dose effects of glipizide given (a) as a rapid-release soft gelatin capsule containing the drug in solution, (b) in conventional tablet, and (c) intravenously. The oral formulations were administered 30 minutes before and the intravenous formulation immediately before standardised breakfasts. The glipizide doses were capsule and tablet 5mg (study 1) and capsule, tablet and IV 2.5mg (study 2). Glipizide levels were measured by liquid chromatography; insulin, proinsulin and C-peptide levels by radioimmunoassay; and blood or plasma glucose levels by a glucose oxidase method. Glipizide absorption was faster from the capsule. Intravenous (2.5mg), capsule and tablet (2.5 and 5mg) administration of glipizide augmented the post-breakfast increase in insulin and C-peptide levels and reduced the post-breakfast hyperglycaemia. Both capsule and tablet (5mg) [study 1] augmented the post-breakfast increase in proinsulin levels, in proportion to those of insulin. Despite the more rapid absorption of glipizide from the capsule compared with the tablet, and despite the immediate rise in glipizide levels following IV administration, there was little difference in serum insulin levels between formulations, and no difference in blood or plasma glucose levels. This contrasts with previous findings in healthy volunteers and in subjects with newly detected NIDDM. The insulin responses in the patients of study 2, who ingested 600 kcal, were more pronounced than in those of study 1, in which patients ingested only 378 kcal, even though the latter had glipizide levels that were 3 times higher. This supports the notion that an increase in sulphonylurea dose cannot compensate for increased energy intake. The net effect of 5mg glipizide on proinsulin levels seemed limited to about 4 to 6 hours, suggesting that this dose would not cause chronic hyperproinsulinaemia.