Drugs online research references
Eur J Clin Pharmacol. 1980 Oct;18(3):279-83.
Influence of food intake on the absorption and effect of glipizide in diabetics and in healthy subjects.
Wahlin-Boll E, Melander A, Sartor G, Schersten B.
The influence of a standardized breakfast on the single dose (5 mg) kinetics and effects of glipizide was examined in 9 healthy volunteers and in 14 diabetics not previously exposed to a sulfonylurea. In the volunteers, glipizide caused an increase in plasma insulin and a reduction in blood glucose both during continued fasting and when the drug was taken with the breakfast. Food intake did not influence the peak concentration, the elimination half-life or the bioavailability of the drug. However, food intake significantly delayed the absorption of glipizide by about 0.5 h. In the patients. glipizide produced a significant increase in plasma glucose in response to the meal. Starting at breakfast and for 45 min thereafter serum glipizide concentrations were significantly higher when the drug was taken 0.5 h before the meal, than when ingested concurrently with it. With the former treatment, the increase in plasma insulin occurred earlier and the blood glucose reduction was pronouncedly greater than with the latter treatment. As the absorption of glipizide may be delayed by concurrent breakfast, this may help to explain, why the administration of glipizide 0.5 h before breakfast led to a more appropriate relation between the serum concentration of the drug and the metabolic impact of the meal, thereby promoting more appropriate insulin release and better glucose disposition than after concurrent intake of the drug and breakfast.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7002565&dopt=Abstract
J Clin Invest. 1981 Apr;67(4):1016-23.
Selective potentiation of insulin-mediated glucose disposal in normal dogs by the sulfonylurea glipizide.
Putnam WS, Andersen DK, Jones RS, Lebovitz HE.
Investigative data have suggested that the extrapancreatic actions of the sulfonylureas may be paramount in their chronic antidiabetic action. The present study examines the effects of chronic sulfonylurea treatment on in vivo insulin action. Peripheral insulin levels, hepatic glucose production (Ra), and overall glucose disposal (Rd) were studied in six awake, normal dogs given both 0.5 and 1.0 mU/kg per min pork insulin for 2.5 h. This produces stable hyperinsulinemia from 15 to 150 min. Fasting euglycemia was held constant by the glucose clamp technique and averaged 99% basal glucose in all studies. Ra and Rd were determined from infusion of [3-(3)H]glucose, begun 90 min prior to insulin infusion. 10 mg of the sulfonylurea glipizide, was given daily to the test animals for the 10 to 20 d following appropriate control studies, then was withheld for 24 h, and the dogs were restudied. Glipizide treatment did not significantly alter basal glucose turnover, Ra, mean glucose values, or mean insulin levels as determined by radioimmunoassay. Increase in Rd above basal glucose turnover in response to insulin (delta Rd) was significantly (P less than 0.05) increased by glipizide treatment at both insulin dosage levels (paired analysis). At 1.0 mU/kg per min insulin, delta Rd rose from 2.6 mg/kg per min before glipizide to 6.5 mg/kg per min after glipizide treatment. At 0.5 mU/kg per min insulin, delta Rd went from 1.1 mg/kg per min before glipizide to 2.2 mg/kg per min after glipizide treatment. Glipizide treatment doubled the effects of insulin on Rd, while showing no significant effect upon insulin suppression of Ra. We conclude that a significant extrapancreatic chronic action of glipizide lies in its ability to selectively potentiate Rd.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7009650&dopt=Abstract
Acta Med Scand Suppl. 1981;656:11-8.
Effects of sulfonylurea on the secretion and disposition of insulin and C-peptide.
Almer LO, Johansson E, Melander A, Wahlin-Boll E.
In an attempt to examine the influence of sulfonylurea on the secretion, disposition and effect of insulin, 9 diabetic patients were studied during three one-month medications with (a) chlorpropamide (t1/2 greater than 24 h) once daily, (b) glipizide (t1/2 2-4 h) once daily, and (c) glipizide in divided dosage. The food intake of each patient was identical during each examination period. Blood concentrations of C-peptide, insulin, glucose, and drugs were determined before and after breakfast and lunch on the 4th day of each examination period. As expected, once-daily administration of glipizide led to higher after-breakfast concentrations of the drug than when the dose was divided. However, the C-peptide changes following breakfast were similar both during these two treatments and also during chlorpropamide, indicating that the amounts of insulin released from the pancreas were equivalent. In spite of this, glipizide once daily yielded 60-70% more insulin in systemic blood following breakfast than did the two other treatments. Reasonably, this signifies that the hepatic extraction of insulin was reduced during once-daily glipizide, allowing more insulin to reach systemic circulation. In addition, this was found to promote a more effective utilization of glucose following breakfast. Following lunch, the C-peptide release, the plasma insulin increase and the blood glucose reduction were greater when glipizide was given in divided dosage than when once-daily glipizide or chlorpropamide was employed. This occurred even though the after-lunch concentration of glipizide in systemic blood was lower rather than higher during divided than during once-daily administration. This supports the notion that the effect of orally administered sulfonylurea is determined not only by its concentration in systemic blood but also by its gastroenterohepatic appearance. Glipizide may offer greater therapeutic flexibility than chlorpropamide, but further studies are required to define the optimum choice and use of sulfonylureas.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7046346&dopt=Abstract
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