Drugs online research references
Eur J Clin Pharmacol. 1975;8(1):63-9.
Comparison of the pharmacokinetics of glipizide and glibenclamide in man.
Balant L, Fabre J, Zahnd GR.
Four subjects received 5 mg 14C-glipizide orally, 3 subjects 1 mg intravenously and 2 subjects 5 mg 14C-glibenclamide orally. Plasma levels of radioactivity, and urinary and faecal excretion were measured. For both drugs the disappearance of radioactivity from plasma followed complex kinetics and the apparent half-lives increased steadily with time. The two sulfonylureas were extensively metabolized and were excreted in the urine as hydroxylated or conjugated metabolites. The effects of both drugs on blood glucose and immunoreactive insulin were comparable. The findings are compared with other published results.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=823030&dopt=Abstract
Biochem Pharmacol. 1993 Nov 2;46(9):1585-90.
Increase in insulin binding and inhibition of the decrease in the phospholipid content of human term placental homogenates in culture by the sulfonylurea glipizide.
Desoye G, Barnea ER, Shurz-Swirsky R.
Department of Obstetrics and Gynecology, University of Graz, Austria.
Term placental explants were cultivated for 48 hr without (control) and with various concentrations of glipizide. Maximum binding of [125I]-insulin in the control samples was decreased after 12 and 24 hr returning to initial values after 48 hr. In the presence of glipizide the binding was generally higher, reaching 180% (557 and 1000 nmol/L) of the corresponding control value (P < 0.01) after 48 hr owing to the presence of nearly 3-fold more (P < 0.05) receptors than in the untreated controls. Tissue cholesterol content was almost unaffected whereas both the phospholipid content and the corresponding phospholipid-to-cholesterol ratios were markedly, and in a time-dependent manner, increased by glipizide as compared to the controls. This was due to decreasing cholesterol and phospholipid concentrations in the controls during the time of culture as compared to initial values, and also to unchanged levels in glipizide-treated cultures. We conclude that glipizide affects placental insulin receptors and the phospholipid content of the tissue.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8240415&dopt=Abstract
Diabete Metab. 1975 Mar;1:13-21.
[Experimental study of glipizide. A comparison with other hypoglycemic sulfonamides (author's transl)]
[Article in French]
Loubatieres AL, Loubatieres-Mariani MM, Alric R, Ribes G, Sorial G, Tarasco A.
Glipizide is a new hypoglycaemic sulphonylurea. In this work we have studied experimentally the hypoglycaemic activity of this drug, its insulin secretory effect and its action on the development of the islets of Langerhans. Studies in the dog: In the normal conscious dog the hypoglycaemic effect of the drug was studied when increasing doses (0,03 mg/kg, 0,05 mg/kg, 0,07 mg/kg and 0,09 mg/kg) were injected intravenously. The hypoglycaemic effect of the drug occurred rapidly, reaching a maximum in about 30 minutes. The relative potency of glipizide was determined in comparison with tolbutamide. Under our experimental conditions, glipizide proved to be on average 99 times more active than tolbutamide when the doses were evaruated by weight; when the doses were expressed in moles it was 163 times more active. Plasma insulin levels manifested an increase at the first minute. This rose rapidly to a maximum at 5 to 15 minutes after the injection. Following this, insulinemia decreased and the values recorded at 60 minutes were about the same as the starting values. There is a linear relation between the logarithm of the dose and the area under the insulin curve measured for the first sixty minutes. After oral administration to the normal dog, glipizide (081 mg/kg and 1mg/kg) provoked a hypoglycemia manifested after a 30 to 60 minutes latent period. With the dose of 1 mg/kg the maximal effect on blood glucose level was reached between 1,30 and 3 hours, depending on the animal. Plasma insulin levels also increased after a latent period which varied from one animal to another. The dogs presenting the earliest increase in insulinemia were those in which glycemia drops most rapidly. Comparison with other sulfonamides (glibenclamide, glisoxepide and tolbutamide) showed that the hypoglycemic action of glipzide was very similar to that of glisoxepide and that it occurred much earlier than with glibenclamide. The insulin secretory effect of glipizide also occurred much earlier than that of glibenclamide, manifesting itself as early as that of glisoxepide and tolbutamide.Studies on the isolated rat pancreas: On the isolated rat pancreas perfused with Krebs-Ringer solution containing glucose (1,5 g/l), glipizide (10 mug/I) considerably increased the amount of secreted insulin. The stimulation of insulin secretion occurred rapidly and persisted powerfully during the entire duration of the infusion. It faded out progressively after stopping the infusion and the secretion remained higher than the control secretion during the following 45 minutes of the experiment. A concentration as low as 0,5 mug/I provoked a distinct increase of insulin secretion. Studies on the development of the islets of langerhans in the mouse: The prolonged administration of glipizide (100 mg/kg daily for 35 days) increased the "insular index", which is directly proportional to the islet weight, by 27%. Therefore this product possesses betacytotrophic activity...
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=824163&dopt=Abstract
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