Effect of oral verapamil on glibenclamide stimulated insulin secretion.

Semple, C. G.; Omile, C. I.; Buchanan, KD; Beastall, G H; Paterson, Ken

doi:10.1111/j.1365-2125.1986.tb05248.x

Cited by 15 publications

(3 citation statements)

References 13 publications

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“…Regarding the major CYP isoform(s) responsible for glibenclamide metabolism, some apparent discrepancies exist. The following in vivo data support the major role of CYP2C9 in the hepatic metabolism of glibenclamide: (i) CYP2C9 polymorphisms significantly affected the pharmacokinetics of glibenclamide (4.9‐fold increase in its exposure in the CYP2C9 *3/*3 genotype compared to the wild type); and (ii) co‐administration of CYP3A inhibitors (clarithromycin, verapamil, or erythromycin) only marginally increased the glibenclamide exposure (by 1.35‐fold or less). Therefore, the estimated f m values of glibenclamide for CYP2C9/CYP3A in the liver were 0.85/0.15, 0.94/0.06, and 1.00/0.0, respectively, when the glibenclamide β value was 0.2, 0.5, and 0.8 (see Supplementary Text, Supplementary Table S2, and Supplementary Figure S3 ).…”

Section: Discussionsupporting

confidence: 57%

Comprehensive PBPK Model of Rifampicin for Quantitative Prediction of Complex Drug‐Drug Interactions: CYP3A/2C9 Induction and OATP Inhibition Effects

Asaumi

Toshimoto²,

Tobe

et al. 2018

CPT Pharmacom & Syst Pharma

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This study aimed to construct a physiologically based pharmacokinetic (PBPK) model of rifampicin that can accurately and quantitatively predict complex drug‐drug interactions (DDIs) involving its saturable hepatic uptake and auto‐induction. Using in silico and in vitro parameters, and reported clinical pharmacokinetic data, rifampicin PBPK model was built and relevant parameters for saturable hepatic uptake and UDP‐glucuronosyltransferase (UGT) auto‐induction were optimized by fitting. The parameters for cytochrome P450 (CYP) 3A and CYP2C9 induction by rifampicin were similarly optimized using clinical DDI data with midazolam and tolbutamide as probe substrates, respectively. For validation, our current PBPK model was applied to simulate complex DDIs with glibenclamide (a substrate of CYP3A/2C9 and hepatic organic anion transporting polypeptides (OATPs)). Simulated results were in quite good accordance with the observed data. Altogether, our constructed PBPK model of rifampicin demonstrates the robustness and utility in quantitatively predicting CYP3A/2C9 induction‐mediated and/or OATP inhibition‐mediated DDIs with victim drugs.

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Section: Discussionsupporting

confidence: 57%

Comprehensive PBPK Model of Rifampicin for Quantitative Prediction of Complex Drug‐Drug Interactions: CYP3A/2C9 Induction and OATP Inhibition Effects

Asaumi

Toshimoto²,

Tobe

et al. 2018

CPT Pharmacom & Syst Pharma

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“…However there was no systematic difference in the formulations taken by those with the highest plasma concentrations, and timing errors alone cannot account for the highest plasma concentrations of glibenclamide seen. Another possible explanation of the high glibenclamide concentrations is sulphonamide and other drug interactions (Ryan & Oyston, 1988;Semple et al, 1986) although their importance is disputed (Sjoberg et al, 1987), and in any case, in-patients were taking more other medications than out-patients. Perhaps a more likely explanation of the higher plasma drug concentrations is 'over-compliance', that is, selfadministration of an excessive dose of drug, by a proportion of out-patients, shortly before their clinic attendances.…”

Section: Discussionmentioning

confidence: 99%

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

Coppack

Lant

McIntosh

et al. 1990

Brit J Clinical Pharma

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1 The pharmacokinetic and pharmacodynamic properties of oral glibenclamide have been studied in 31 hospitalised in-patients and 79 ambulant out-patients with diabetes mellitus. 2 Breakfast was found to have no significant influence on the kinetic behaviour of glibenclamide or on the effect of this drug on blood glucose utilisation. 3 The time course of glibenclamide kinetics after 20 mg dosing was adequately described by a two-compartment open model, yielding mean half-lives of 3.3 ± 1.5 h (t½/,X) and 9.7 ± 1.2 (t½,z) for the initial and terminal elimination phases respectively. 4 No significant accumulation or change in kinetic profile occurred in patients who had normal renal and hepatic function, were treated continuously with glibenclamide, and then rechallenged after 8-12 weeks.5 Despite inter-individual variations in drug absorption, peak plasma concentrations (Cmax) and the area under the plasma concentration-time curve (AUC(0-24)) were dosedependent over the dose range 5-20 mg. No significant dose-response behaviour was observed in respect of glucose utilisation, suggesting that there is little clinical benefit in using doses of glibenclamide above 5 mg day-'. 6 Comparison of plasma glibenclamide concentrations at different time-bands following doses of 5 and 10 mg showed a wider range in ambulant out-patients than in age-, sexmatched in-patients treated with the same dosages of drug. Mean plasma drug concentrations attained at all time bands up to 8 h after dosing were higher in out-patients than in in-patients, suggesting a tendency to 'over-compliance' by patients in anticipation of attendance at clinic.

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“…Glibenclamide is both a substrate and inhibitor of P‐glycoprotein in vitro [9]. In previous in vivo studies rifampicin has reduced and verapamil increased the plasma concentrations of glibenclamide [6, 29]. A recent study with human embryonic kidney cells, stably expressing OATP2B1, suggested that glibenclamide was also a substrate for this transporter expressed, for example, in the intestine and liver [7].…”

Section: Discussionmentioning

confidence: 99%

Effects of clarithromycin and grapefruit juice on the pharmacokinetics of glibenclamide

Lilja

Niemi

Fredrikson

et al. 2007

Brit J Clinical Pharma

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What is already known about this subject • Severe hypoglycaemia has been reported after concomitant use of clarithromycin and glibenclamide. • Glibenclamide is a substrate for the transporters P‐glycoprotein and OATP2B1. • Clarithromycin inhibits P‐glycoprotein and grapefruit juice inhibits OATP2B1. What this study adds • Clarithromycin increases the plasma concentration of glibenclamide. • A pharmacokinetic interaction may explain reported hypoglycaemia during simultaneous administration of clarithromycin and glibenclamide. • Grapefruit juice has no effect on the pharmacokinetics of glibenclamide. Aims Case reports suggest that clarithromycin can increase the glucose‐lowering effect of glibenclamide which is metabolized mainly by CYP2C9 and is a substrate for P‐glycoprotein and OATP2B1. Our objective was to evaluate whether the P‐glycoprotein inhibitor, clarithromycin, increases and the putative OATP2B1 inhibitor, grapefruit juice, decreases plasma concentrations of glibenclamide. Methods In a randomized three‐phase crossover study, 12 subjects ingested 250 mg clarithromycin or placebo twice daily or 200 ml grapefruit juice three times daily for 2 days. On day 3, they ingested 0.875 mg glibenclamide with sugar water or grapefruit juice. Concentrations of glibenclamide and clarithromycin in plasma, glucose in blood, and excretion of hydroxyglibenclamide into urine were measured up to 12 h. Results Clarithromycin increased the peak concentration (Cmax) of glibenclamide to 1.25‐fold (95% confidence interval (CI) 1.12, 1.40; P < 0.01) and the area under the plasma concentration‐time curve to 1.35‐fold (95% CI 1.21, 1.50; P < 0.01) compared with the placebo phase. The time to Cmax, the half‐life of glibenclamide, and the amount of hydroxyglibenclamide excreted into urine remained unaltered. Grapefruit juice did not change the pharmacokinetics of glibenclamide. Clarithromycin concentrations implied a good compliance. Blood glucose did not deviate between the phases. Conclusions Clarithromycin increased plasma concentrations of glibenclamide, possibly by inhibiting P‐glycoprotein in the intestinal wall. Although not seen with the present study design, clarithromycin may enhance the effect of glibenclamide by increasing plasma glibenclamide concentrations, which warrants close monitoring of blood glucose during their co‐administration. Grapefruit juice had no effect on glibenclamide pharmacokinetics.

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Effect of oral verapamil on glibenclamide stimulated insulin secretion.

Cited by 15 publications

References 13 publications

Comprehensive PBPK Model of Rifampicin for Quantitative Prediction of Complex Drug‐Drug Interactions: CYP3A/2C9 Induction and OATP Inhibition Effects

Comprehensive PBPK Model of Rifampicin for Quantitative Prediction of Complex Drug‐Drug Interactions: CYP3A/2C9 Induction and OATP Inhibition Effects

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

Effects of clarithromycin and grapefruit juice on the pharmacokinetics of glibenclamide

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