Drugs online research references
Acta Endocrinol Suppl (Copenh). 1980;239:44-52.
Diurnal pattern of plasma insulin and blood glucose during glibenclamide and glipizide therapy in elderly diabetics.
Groop L, Harno K.
The effect of a single and a split dose of glibenclamide and glipizide on the diurnal levels of blood glucose and plasma insulin were compared in 15 insulin-independent diabetics. The patients were treated for two weeks with a) glibenclamide or glipizide 5 mg b.i.d., b) diet alone, c) glibenclamide or glipizide 7.5 mg o.d., and d) crossing over of c). The patients were on isocaloric diet and the diurnal levels of blood glucose and plasma insulin were determined after each period. As compared to the diet, the single morning dose of both drugs reduced the blood glucose values to the same extent (p < 0.001) without any effect on corresponding insulin-levels. The single morning dose was sufficient to provide adequate blood glucose control for up to 24-hours. There was no further benefit of the (even greater) split doses. In accordance with the augmented physiologic insulin release in the morning, a single morning dose of sulfonylureas may be the preferable dosage regimen in the treatment of elderly insulin-independent diabetics of moderate degree.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6776763&dopt=Abstract
Acta Med Scand. 1980;208(4):301-7.
Comparative single-dose kinetics and effects of four sulfonylureas in healthy volunteers.
Sartor G, Melander A, Schersten B, Wahlin-Boll E.
The single-dose kinetics and effects of tolbutamide (500 mg), chlorpropamide (250 mg), glibenclamide (5 mg) and glipizide (5 mg) were compared in 7 healthy male volunteers by measurements of serum concentrations of the drugs and of plasma insulin and blood glucose. The drugs were administered both on an empty stomach and together with a standardized breakfast. The concentrations of tolbutamide and chlorpropamide were measured by gas chromatography, those of glipizide with high-pressure liquid chromatography, those of glibenclamide and insulin by radioimmunoassay and those of glucose by the hexokinase method. Glipizide and glibenclamide were more potent inducers of insulin release and blood glucose reduction than tolbutamide and chlorpropamide. As the concentrations of the former two drugs were in the range of nmol/l and those of the latter two in the mumol/l range, the findings support the notion that the intrinsic activity of the two second-generation sulfonylureas is at least 1 000 times greater than that of the two first-generation drugs. Glipizide seemed to be a more potent and more rapid insulin releaser than glibenclamide, but this may be secondary to biopharmaceutic differences between the two preparations. The bioavailability of glipizide was apparently greater than that of glibenclamide. Both glibenclamide (t 1/2 = 1.8 h) and glipizide (t 1/2 = 4.3 h) showed much shorter elimination half-lives than tolbutamide (7 h) and chlorpropamide (34 h). It seems probable, however, that these half-lives are not fully informative as to the duration of action of the drugs.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6778079&dopt=Abstract
Am J Med. 1981 Feb;70(2):361-72.
The pharmacology of sulfonylureas.
Skillman TG, Feldman JM.
In this report we review the pharmacology of the hypoglycemic sulfonylurea drugs. The early work with sulfonylureas is briefly described. The pharmacokinetics of first-generation sulfonylureas, such as tolbutamide, chlorpropamide, acetohexamide and tolazamide, are described. The first-generation sulfonylureas are compared with second-generation sulfonylureas such as glyburide, glipizide and glibornuride. These latter drugs have a more nonpolar or lipophilic side chain, which results in a marked increase in their hypoglycemic potency. Because of the low serum concentration required for effective therapy, it is necessary to measure the serum concentration of second-generation sulfonylureas by gas-liquid chromatography or radioimmunoassay. The second-generation sulfonylureas do not produce facial flushing after ethanol ingestion (Antabuse effect) and are not uricosuric. Glyburide (but not glipizide or glibornuride) has been evaluated for its effect on water excretion. Glyburide not only does not increase water retention but in fact also increases free water clearance. The second-generation sulfonylureas bind to human serum albumin by nonionic forces in contrast with tolbutamide and chlorpropamide which bind by ionic forces. Thus, anionic drugs such as phenylbutazone, warfarin and salicylate do not displace glyburide from albumin as they displace tolbutamide and chlorpropamide. Therefore, it may be safer to administer the second-generation sulfonylureas than the more polar sulfonylureas when concurrent administration of other pharmacologic agents is likely. The sulfonylurea drugs lower plasma glucose concentrations in diabetic patients by stimulating insulin secretion and by potentiating the biologic effect of the insulin on such tissues as skeletal muscle, fat and liver. The mechanism of the latter so-called extra-pancreatic effect may be activated by increasing the deficient numbers of insulin receptors on muscle, fat or liver cells.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6781341&dopt=Abstract
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