Behaviour of glibenclamide on repeated administration to diabetic patients

Balant, L; Zahnd, G; Weber, Frank; Fabré, J

doi:10.1007/bf00561783

Cited by 48 publications

(30 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Significant prolongation in the elimination half-life [38][39][40] and an increased volume This study was supported in parts by grants from The Swedish Academy of Pharmaceutical Sciences (Gunnar of distribution of Gb has also been observed during chronic dosing [40]. In addition, a recent study indicates that the Hylténs Memory Fund) and Apoteksbolaget AB (The…”

Section: And M2 (P=006) the Resulting Parameters After Linearmentioning

confidence: 99%

Concentration-effect relations of glibenclamide and its active metabolites in man: modelling of Pharmacokinetics and Pharmacodynamics

Rydberg¹,

Jönsson²,

Karlsson³

et al. 1997

Br J Clin Pharmacol

View full text Add to dashboard Cite

Aims The main purpose of this paper is to describe the relationship between serum concentrations of glibenclamide and its main metabolites and the effects on blood glucose levels, the clinically most relevant parameter to assess in diabetes. Methods Serum concentrations and blood glucose lowering effects (expressed as percent blood glucose reduction vs placebo) of glibenclamide (Gb) and its active metabolites, 4-trans-hydroxy-(M1) and 3-cis-hydroxy-glibenclamide (M2), were analysed in eight healthy subjects participating in a placebo-controlled, randomized, single-blind crossover study, using intravenous administration of each compound as well as oral administration of Gb. Results Plots of % blood glucose reduction vs log serum concentration demonstrated counter-clockwise hysteresis for parent drug and its metabolites. An effect compartment was linked to appropriate pharmacokinetic models and pharmacokinetic and pharmacodynamic modelling was used to fit the pharmacokinetics of Gb by both routes and the metabolites for each individual. Based on the individual concentration-time profiles a PK/PD-model was applied to all effect data simultaneously. An increase in the steady-state serum concentration when the effect is 50% of maximal, CE ss50, , was found in the sequence M1 (23 ng ml −1 ), M2 (37 ng ml −1 ) and Gb (108 ng ml −1 ). Corresponding interindividual variabilities expressed as CV% were 25%, 47% and 26%. The elimination rate constants from the effect site (k E0 ) were estimated and increased in the order M1 (0.178 h −1 , CV 13%), M2 (0.479 h −1 , CV 8.5%) and Gb (1.59 h −1 , CV 36%). Corresponding equilibration half-lives for the effect site (k E0-HL ) were 3.9 h, 1.4 h and 0.44 h. Estimated E max -values obtained for M1, M2 and Gb were 40% (CV 30%), 27% (CV 56%) and 56% (CV 14%), respectively. Conclusions It is concluded that the two major metabolites of Gb are hypoglycaemic in man, that they may have higher activity at low concentrations and that they may have a longer effect duration than the parent drug.

show abstract

Section: And M2 (P=006) the Resulting Parameters After Linearmentioning

confidence: 99%

Concentration-effect relations of glibenclamide and its active metabolites in man: modelling of Pharmacokinetics and Pharmacodynamics

Rydberg¹,

Jönsson²,

Karlsson³

et al. 1997

Br J Clin Pharmacol

View full text Add to dashboard Cite

show abstract

“…In Italy, breakfast is usually light, whereas the midday meal is the largest of the day: it is therefore not surprising that a schedule widely used by family doctors consists in giving small doses of OHA (i. e. half a tablet) before breakfast and/or supper and a larger dose (i. e. one tablet) before the midday meal. This type of prescription reflects more the amount of food to be eaten immediately after than the pharmacokinetic properties of glibenclamide: this drug, in fact, shows a relatively short half-life [16] but a slowly equilibrating deep compartment [17]. On repeated dosing, there is a potential risk of multiple overlaps of the drug action [17].…”

Section: Discussionmentioning

confidence: 99%

Occurrence of low blood glucose concentrations during the afternoon in Type 2 (non-insulin-dependent) diabetic patients on oral hypoglycaemic agents: importance of blood glucose monitoring

et al. 1991

View full text Add to dashboard Cite

Summary.The European NIDDM Policy Group states that the lowest target for good control of Type 2 (non-insulin-dependent) diabetic patients is a blood glucose level 4.4 mmol/1, both fasting and postprandially. The aim of this study is to evaluate the occurrence and temporal distribution of values under this target in the clinical records of 463 Type 2 diabetic patients, treated by diet or diet and oral hypoglycaemic agents, monitored for at least 2 years. The protocol includes blood glucose measurements after overnight fasting (08.00 hours), 120-150 rain after breakfast (11.00 hours) and 120 and 240 min after lunch (14.00 and 16.00 hours). At least one blood glucose concentration of less than 4.4 mmol/1 was presented by 42% of the patients. The only difference between patients showing and not showing glycaemic levels under this target was the higher percentage on oral hypoglycaemic agents in the first group (68.4% vs 56.9% ,p = 0.016). We considered 299 blood glucose profiles containing at least one value of less than 4.4 retool/l, observing that a) 46.9% of profiles from patients treated by diet alone and 68.7% of profiles from patients treated both by diet and oral hypoglycaemic agents presented the lowest blood glucose concentration at 16.00 hours (p = 0.002). b) No correlation existed between fasting blood glucose and values at 16.00 hours in profiles from diet-treated patients, whereas a negative correlation was present in patients on diet and oral hypoglycaemic agents, indicating that an excess of oral agents, administered to correct fasting hyperglycaemia, was the cause of the low glycaemic values in the afternoon, c) 37.9% of profiles on a diet and 83.3% of profiles on diet and oral agents showed fasting glucose concentrations > 6.7 mmol/1, the upper limit of good control according to the European NIDDM Policy Group. This indicates that fasting hyperglycaemia does not exclude the occurrence of low glucose values throughout the day and that it is necessary to monitor blood glucose profiles.

show abstract

“…Some studies have measured total radioactivity after giving radiolabelled drug (Balant et al, 1975;Rupp et al, 1972); others have determined immunoreactive glibenclamide (Balant et al, 1977) or employed high performance liquid chromatography (Rogers et al, 1982;WahlinBoll & Melander, 1979) or gas liquid chromatography (Castoldi & Tofanetti, 1979). Use of radioimmunoassay over-estimates glibenclamidederived plasma activity because of crossreactions with hydroxylated metabolites (Pearson, 1985).…”

Section: Discussionmentioning

confidence: 99%

“…drug assay, and cannot therefore account for the more striking differences in response noted between patients. The possibility of drug accumulation during chronic administration was raised by the findings of Balant et al (1977), but may represent the significant contribution after multiple dosing of less-active glibenclamide metabolites to the drug assay. Our results showed no evidence of drug accumulation after repeated challenge with the same dose of glibenclamide for up to 12 weeks.…”

Section: Discussionmentioning

confidence: 99%

“…The effect of food on the bioavailability of glibenclamide is unclear, some reports showing no effect (Sartor et al, 1980a), whilst others demonstrate distinct alterations in drug absorption (Balant et al, 1977). The result is that standard advice on when the drug should best be given, in relation to breakfast, varies (British National Formulary, 1989;George, 1984).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Coppack

Lant

McIntosh

et al. 1990

Brit J Clinical Pharma

View full text Add to dashboard Cite

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.

show abstract

Behaviour of glibenclamide on repeated administration to diabetic patients

Cited by 48 publications

References 8 publications

Concentration-effect relations of glibenclamide and its active metabolites in man: modelling of Pharmacokinetics and Pharmacodynamics

Concentration-effect relations of glibenclamide and its active metabolites in man: modelling of Pharmacokinetics and Pharmacodynamics

Occurrence of low blood glucose concentrations during the afternoon in Type 2 (non-insulin-dependent) diabetic patients on oral hypoglycaemic agents: importance of blood glucose monitoring

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

Contact Info

Product

Resources

About