Drugs online research references
Am J Physiol. 1983 Apr;244(4):E380-4.
Stimulation of pancreatic polypeptide secretion in the dog by hypoglycemic agent HB 699.
Ribes G, Trimble ER, Wollheim CB, Blayac JP, Loubatieres-Mariani MM.
HB 699 is a hypoglycemic agent that has a structural similarity to glibenclamid but does not contain the sulfonylurea group. We have studied the effects of HB 699 and the sulfonylurea glipizide on pancreatic polypeptide (PP) and insulin secretion in the dog. Both HB 699 and glipizide stimulated insulin release and caused hypoglycemia in normal dogs. The secretion of PP was stimulated by HB 699 before the onset of hypoglycemia, whereas, following glipizide administration, PP secretion increased only after the onset of hypoglycemia. As expected, in alloxan-diabetic dogs neither substance affected plasma insulin or blood glucose levels. There was, however, a stimulation of PP secretion by HB 699 that was not observed with glipizide. It appears therefore that HB 699, in contrast to glipizide, stimulates PP secretion in the absence of any changes in circulating glucose and insulin concentrations. The direct action of HB 699 on the pancreas was shown by stimulation of insulin and PP secretion in the in vitro perfused uncinate process. In view of its direct pancreatic actions, HB 699 may prove a useful tool for further study of PP secretory mechanisms.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6340523&dopt=Abstract
Int J Clin Pharmacol Ther Toxicol. 1983 Feb;21(2):98-107.
Pharmacokinetics and pharmacodynamics of glipizide in healthy volunteers.
Pentikainen PJ, Neuvonen PJ, Penttila A.
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.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6341263&dopt=Abstract
Diabetologia. 1983 Jun;24(6):441-4.
Sulphonylureas in vitro do not alter insulin binding or insulin effect on amino acid transport in rat hepatocytes.
Dolais-Kitabgi J, Alengrin F, Freychet P.
The effects of four sulphonylureas (gliclazide, glibenclamide, chlorpropamide and glipizide) on insulin binding and insulin action were studied in vitro using primary cultured rat hepatocytes. Cells were cultured for 20 h in the absence or presence of the sulphonylurea. The binding of insulin to rat hepatocyte monolayers was not altered in cells previously exposed to gliclazide at 0.7, 7.0 or 70 micrograms/ml; and to glibenclamide, chlorpropamide, or glipizide at 0.1, 1.0 and 10 micrograms/ml. Insulin-induced down regulation was not affected by a simultaneous exposure of hepatocyte monolayers to any of the four agents. The stimulatory effect of insulin on alpha-aminoisobutyric acid uptake by the cells was not modified following exposure to the drugs. These studies indicate that the sulphonylureas tested do not have a direct effect on insulin receptors in hepatocytes; and that, in vitro, they do not alter the post-receptor events involved in the insulin-induced stimulation of amino acid transport in these cells.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6350080&dopt=Abstract
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