Pharmacokinetic and pharmacodynamic studies of glibenclamide in non‐ insulin dependent diabetes mellitus.

Coppack, SW; Lant, A. F.; McIntosh, C.; Rodgers, AV

doi:10.1111/j.1365-2125.1990.tb03688.x

Cited by 82 publications

(50 citation statements)

References 40 publications

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“…Significantly greater lowering of blood glucose was reported by Sartor et al (1982), while no beneficial effects on blood glucose utilisation were observed in the recent study of Coppack et al (1990). Bruce et al (1988) presented evidence in support of the importance of the timing of insulin secretion in relation to meal intake.…”

Section: Discussionmentioning

confidence: 57%

The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations.

Neuvonen

Kivistö

1991

Brit J Clinical Pharma

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1 The effect of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations was investigated in healthy volunteers in two separate studies, using a randomized cross-over design with two phases. 2 A single dose of magnesium hydroxide (850 mg) or water only (150 ml) was given immediately after the ingestion of a micronised (1.75 mg, seven subjects) or a nonmicronised (2.5 mg, six subjects) preparation of glibenclamide. Plasma concentrations of glibenclamide, insulin and glucose were measured. 3 Magnesium hydroxide accelerated (P < 0.05) the absorption of glibenclamide from the micronised preparation to a small extent but the extent of absorption and the insulin and glucose responses were unaltered. 4 Coadministration of magnesium hydroxide with the non-micronised glibenclamide preparation increased the area under the plasma glibenclamide concentration-time curve from 0 to 3 h, five-fold (P < 0.05), the total area three-fold (P < 0.05) and the peak drug concentration three-fold (P < 0.05). The incremental insulin area from 0 to 3 h was increased 35-fold (P < 0.05) and the maximum insulin response 10-fold (P < 0.05) by magnesium hydroxide. 5 Concomitant ingestion of magnesium hydroxide and non-micronised glibenclamide may greatly enhance the absorption and efficacy of glibenclamide. The absorption of micronised glibenclamide appears to be only slightly influenced by magnesium hydroxide.

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Section: Discussionmentioning

confidence: 57%

The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations.

Neuvonen

Kivistö

1991

Brit J Clinical Pharma

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“…This infusion rate leads to local forearm glibenclamide concentrations which are similar to systemic concentrations as reached daily during the treatment of NIDDM [20,21]. In this way the effect of therapeutic glibenclamide concentrations on the forearm vasodilator response to ischaemia was assessed locally.…”

Section: Methodsmentioning

confidence: 99%

“…Because of the long half-life, high protein binding [20,21] and possible incorporation of sulphonylurea derivatives in the plasma membrane [22], randomization of placebo and glibenclamide infusion was not possible because of carry-over effects.…”

Section: Methodsmentioning

confidence: 99%

“…Insulin ranged from 7.5 ± 0.8 to 8.1 ± 1.0 mU/l, C-peptide ranged from 0.38 ± 0.04 to 0.43 ± 0.04 nmol/l and glucose ranged from 4.2 ± 0.2 to 4.5 ± 0.1 mmol/l. Local glibenclamide concentrations varied from 65 ± 7 to 53 ± 5 ng/ ml during the test and remained within a therapeutic range, while systemic glibenclamide concentrations were maximally 11.6 ± 1.2 ng/ml at the end of the experiment, and remained below the therapeutic range as demonstrated by unchanged insulin levels [20,21].…”

Section: Effect Of Glibenclamide On Responses To Ischaemiamentioning

confidence: 99%

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Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans

et al. 1996

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In 1983, Noma [1] was the first to describe that an outward potassium current increased significantly when guinea pig or rabbit cardiac muscle cells were subjected to hypoxia. This current was caused by the activation of potassium channels, which was independent of the intracellular Ca 2+ concentration, but dependent on the intracellular concentration of adenosine-5 ′-triphosphate ([ATP] i ). These so-called ATPsensitive potassium (K ATP ) channels were suggested to play a cardioprotective role during ischaemia. Later, K ATP channels were also found in skeletal muscle [2], smooth muscle [3] and pancreatic beta cells [4] from animals. In pancreatic beta cells the K ATP channels mediate insulin secretion [5] and are a target for sulphonylurea derivatives in the treatment of non-insulin-dependent diabetes mellitus (NIDDM) [6]. Sulphonylurea derivatives are highly specific in blocking pancreatic and cardiovascular K ATP channels, and Diabetologia (1996Diabetologia ( ) 39: 1562Diabetologia ( -1568 Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans Summary Experimental data show that ATP-sensitive potassium (K ATP ) channels not only occur in pancreatic beta cells, but also in the cardiovascular system, where they mediate important cardioprotective mechanisms. Sulphonylurea derivatives can block the cardiovascular K ATP channels and may therefore interfere with these cardioprotective mechanisms. Therefore, it is of clinical importance to investigate whether sulphonylurea derivatives interact with vascular K ATP channels in humans. Using venous-occlusion strain-gauge plethysmography, we investigated whether ischaemia-induced reactive hyperaemia is reduced by the sulphonylurea derivative glibenclamide in 12 healthy male non-smoking volunteers. Forearm vasodilator responses to three periods of arterial occlusion (2, 5 and 13 min) during concomitant infusion of placebo into the brachial artery were compared with responses during concomitant intra-arterial infusion of glibenclamide (0.33A control study (n = 6) showed that time itself did not change the vasodilator response to ischaemia.Glibenclamide significantly increased minimal vascular resistance (from 2.1 ± 0.1 to 2.3 ± 0.2 arbitrary units, Student's t-test: p = 0.01), and reduced mean forearm blood flow (from 37.5 ± 2.0 to 35.4 ± 2.0 ml ⋅ min -1 ⋅ dl -1 after 13 min occlusion, ANOVA with repeated measures: p = 0.006) and flow debt repayment during the first reperfusion minute (ANOVA with repeated measures: p = 0.04). In contrast, total flow debt repayment was not affected. Infusion of glibenclamide into the brachial artery resulted in local concentrations in the clinically relevant range, whereas the systemic concentration remained too low to elicit hypoglycaemic effects. Our results suggest that therapeutic concentrations of glibenclamide induce a slight but significant reduction in the early and peak vasodilation during reactive hyperaemia.

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“…To determine the potential role of K ATP channels in regulation of myocardium and coronary artery, glibenclamide (10 mg) was orally administered 60 minutes before catheterization with a continuous infusion of 10% dextrose at the same time. This dose of glibenclamide will result in an estimated serum concentration of 500 nmol/L, 17 which has been shown to block myocardial and vascular K ATP channels in humans. 18 To further confirm whether IP is mandatory for estrogen-induced attenuated vasoconstriction, a group treated with estrogen immediately after the second balloon deflation was assessed.…”

Section: Subjectsmentioning

confidence: 99%

Differential Role of K _ATP Channels Activated by Conjugated Estrogens in the Regulation of Myocardial and Coronary Protective Effects

2003

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Background-We have demonstrated that estrogen can reduce myocardial injury in ischemia-reperfusion via activation of ATP-sensitive potassium (K ATP ) channels. We sought to determine whether the protective effect of estrogen extends to epicardial coronary artery with attenuated vasoconstriction in patients after angioplasty by activation of such channels. Methods and Results-The study was designed to prospectively investigate 41 consecutive patients scheduled for elective coronary angioplasty. Pretreatment with estrogen limited myocardial ischemia during coronary occlusion and attenuated postangioplasty coronary vasoconstriction at the dilated and distal segments. An inhibitor of K ATP channels, glibenclamide, did not affect coronary vasomotor response, although it abolished the beneficial effect of estrogen on myocardial ischemia. Patients to whom estrogen was administered after the second balloon deflation experienced a similar magnitude of myocardial ischemia as controls but showed significantly attenuated vasoconstriction compared with controls (Pϭ0.0001). Endothelin-1 levels from the great cardiac vein rose significantly from 1.9Ϯ0.4 to 3.1Ϯ0.6 pg/mL (Pϭ0.001) 15 minutes after angioplasty in the control group; this was attenuated after estrogen was administered. Significant correlation was found between the changes in coronary vasomotion of the dilated segment and endothelin-1 levels (rϭ0.65, PϽ0.0001). Conclusions-These results demonstrate that estrogen is protective against both myocardial ischemia and coronary vasoconstriction through different mechanisms. The myocardial effect of estrogen was abolished by glibenclamide, which suggests that the cardioprotective effect of estrogen may result from activation of K ATP channels. In contrast, estrogen-induced attenuated vasoconstriction is associated with an attenuated release of endothelin-1, independent of K ATP activation.

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Pharmacokinetic and pharmacodynamic studies of glibenclamide in non‐ insulin dependent diabetes mellitus.

Cited by 82 publications

References 40 publications

The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations.

The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations.

Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans

Differential Role of K _ATP Channels Activated by Conjugated Estrogens in the Regulation of Myocardial and Coronary Protective Effects

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Pharmacokinetic and pharmacodynamic studies of glibenclamide in non‐ insulin dependent diabetes mellitus.

Cited by 82 publications

References 40 publications

The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations.

The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations.

Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans

Differential Role of K ATP Channels Activated by Conjugated Estrogens in the Regulation of Myocardial and Coronary Protective Effects

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Product

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Differential Role of K _ATP Channels Activated by Conjugated Estrogens in the Regulation of Myocardial and Coronary Protective Effects