Pharmacodynamic aspects of two sulphonylurea derivatives glipizide and glibenclamide

Artini, Domenico; Abbiati, R.; Orsini, Gaetano; Parenti, M; Bloch, Konstantin; Daturi, S.; Mandelli, V.

doi:10.1007/bf01218440

Cited by 15 publications

(9 citation statements)

References 7 publications

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“…In this respect, glipizide would appear as a more suitable agent than glibenclamidc or glimepiride [1][2][3] to cause transient stimulation of insulin release. Likewise, in our static experi ments.…”

Section: Discussionmentioning

confidence: 99%

“…potent hypoglycemic sulfonylureas, such as glibenclamide and glimepiride. cause, in perifused islets, a sustained increment in insulin secretion which persists after removal of the drug from the perifusate [1][2][3]. In other cases, it was claimed that a single administration of a hypoglycemic sulfonylurea may render the B cell refractory to a second stimulation by the same agent, in a phenomenon of tachy phylaxis [4], At variance with these observa tions, the present study demonstrates that gli pizide is able to evoke transient, instead of persistent, and iterative stimulation of iso lated rat pancreatic islets.…”

Section: Introductionmentioning

confidence: 99%

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Iterative Stimulation of Pancreatic Islets by Glipizide

Malaisse¹,

Lebrun²

1993

Pharmacology

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Iterative administrations of glipizide (2 μmol/l) for 10 min each to perifused rat pancreatic islets provoked at low glucose concentration (2.8 mmol/l) rapid and rapidly reversible decreases in ⁸⁶Rb outflow, rapid and rapidly reversible increases in ⁴⁵Ca outflow and modest stimulations of insulin release. In the presence of Ca²⁺, the reascension in ⁸⁶Rb outflow was preceded by a transient fall in effluent radioactivity upon withdrawal of the sulfonylurea. At a higher concentration of D-glucose (8.3 mmol/l), glipizide provoked, each time, biphasic and rapidly reversible increases in both ⁸⁶Rb and ⁴⁵Ca outflow, as well as in insulin release. These results are compatible with the view that glipizide decreases K⁺ conductance, leading to depolarization of the B-cell plasma membrane and gating of voltage-sensitive Ca²⁺ channels. In the presence of 8.3 mmol/l D-glucose, however, the inhibitory effect of glipizide on effluent K⁺ permeability may be masked by activation of Ca²⁺-sensitive K⁺ channels. The present data also indicate that glipizide is able to evoke, at the occasion of iterative administrations, biphasic ionic and secretory responses, without evidence of tachyphylaxis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Iterative Stimulation of Pancreatic Islets by Glipizide

Malaisse¹,

Lebrun²

1993

Pharmacology

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“…Compared with glibenclamide, the insulin secretion after glipizide given orally in combination with food starts earlier and is of shorter duration (1, 7, 8, 16, 21). Also the effect on the blood glucose concentration is faster after glipizide (1,19). The sustained effect on insulin secretion after glibenclamide is not merely an effect of delayed intestinal absorption, as it is found also after intravenous administration of the drug (1).…”

Section: Discussionmentioning

confidence: 99%

Glibenclamide and Glipizide in Maturity Onset Diabetes

Blohmé

Waldenström

1979

Journal of Internal Medicine

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The effects of glibenclamide and glipizide on the concentrations of S‐glucose, S‐insulin and S‐lipids and on the 24‐hour urinary glucose excretion were studied in 37 patients with maturity onset diabetes. A double‐blind, cross‐over, double‐dummy technique was used. The fasting S‐insulin concentration was higher during glibenclamide therapy, while the increase in insulin concentration one hour postprandially was stronger during glipizide therapy, supporting the concept that glibenclamide has a more prolonged and glipizide a more fast‐acting effect on insulin secretion. The S‐glucose concentration was lower in the fasting state as well as one hour postprandially during glibenclamide therapy which, together with a lower 24‐hour urinary glucose excretion, indicates that glibenclamide has a stronger blood glucose‐lowering effect. Although statistically significant, the differences were marginal from a clinical point of view. The lipid levels remained unchanged.

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“…The insulin-stimulating potency was thus of the same order as that of glibenc1amide. In the isolated perfused rat pancreas preparation, glipizide resulted in a more rapid onset and offset of insulin secretion than glibenclamide (Artini et al 1973), perhaps because the latter accumulates progressively in {1-cells . In subjects with non-insulindependent diabetes, glipizide increased the blood insulin concentration and reduced the blood glucose concentration .…”

Section: Relevant Pharmacodynamicsmentioning

confidence: 97%

The Relationship Between the Pharmacokinetics and Pharmacodynamic Effects of Oral Hypoglycaemic Drugs

Ferner

Chaplin

1987

Clinical Pharmacokinetics

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Oral hypoglycaemic drugs have widely differing pharmacokinetic properties. Possible pharmacodynamic benefits include greater efficacy and fewer adverse effects. In general, it has not been possible to demonstrate unequivocal differences in clinical efficacy between the sulphonylureas during long term use, although there are clear differences in potency. These differences have been emphasised to the extent that the term 'second-generation' has been used for the most potent sulphonylureas, but there is little to suggest that potency is of any therapeutic significance. Trials to study differences in efficacy have rarely been of acceptable design. They have often used fixed doses of drugs, begging the question of whether true potency ratios have been established for chronic treatment. They have rarely involved substantial numbers of patients in double-blind crossover studies with a suitable washout period. Trials which show that there is a clear relationship between drug concentrations in blood and drug effects (whether therapeutic effects or adverse effects such as severe hypoglycaemia) are generally lacking. Qualitative and semiquantitative analysis of adverse effects supports the concept that drugs with a long half-life (e.g. chlorpropamide), renally excreted active metabolites (e.g. acetohexamide) or unusual properties (e.g. glibenclamide, which accumulates progressively in islet tissue) are more likely to cause prolonged hypoglycaemia, which may be fatal. The major adverse effect of treatment with biguanides is lactic acidosis, and this probably occurs more commonly in patients treated with phenformin than those treated with metformin because of pharmacogenetic variation in phenformin metabolism. The available evidence therefore favours the use of drugs with a short elimination half-life which are extensively metabolised and which have no active metabolites.

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Pharmacodynamic aspects of two sulphonylurea derivatives glipizide and glibenclamide

Cited by 15 publications

References 7 publications

Iterative Stimulation of Pancreatic Islets by Glipizide

Iterative Stimulation of Pancreatic Islets by Glipizide

Glibenclamide and Glipizide in Maturity Onset Diabetes

The Relationship Between the Pharmacokinetics and Pharmacodynamic Effects of Oral Hypoglycaemic Drugs

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