Assessment of single-dose benzodiazepines on insulin secretion, insulin sensitivity and glucose effectiveness in healthy volunteers: a double-blind, placebo-controlled, randomized cross-over trial [ISRCTN08745124]

BMC Clinical Pharmacology

Pierre Petit²  Jean-Frédéric Brun⁴  Bruno Lacarelle¹  Nathalie Molinier³  Isabelle Mourand²  Hugues Chevassus² 

[1] Department of Pharmacokinetics, La Timone University Hospital, Marseille, France;Center for Pharmacology and Health Biotechnology, CNRS UMR 5160, Montpellier, France;Clinical Investigation Center, Saint-Eloi University Hospital, Section of Clinical Pharmacology, Montpellier, France;Department of Clinical Physiology, Lapeyronie University Hospital, Montpellier, France

关键词: diabetes;    glucose tolerance;    insulin sensitivity;    insulin secretion;    clinical investigation;    benzodiazepine;   

Others  :  1085425
DOI  :  10.1186/1472-6904-4-3

 received in 2003-04-03, accepted in 2004-03-04,  发布年份 2004

【 摘 要 】

Background

The present study aimed at investigating in healthy volunteers the effects of diazepam and clonazepam on beta-cell function, insulin sensitivity and glucose effectiveness based on the frequently sampled intravenous (0.5 gkg^-1) glucose tolerance test with minimal-model analysis.

Methods

The study was designed as a double-blind, placebo-controlled, cross-over clinical trial. Diazepam (10 mg) and clonazepam (1 mg) were infused during 30 min to 15 male subjects with a mean age of 22 years (range: 20–29), after informed consent was given. Benzodiazepines were assayed by capillary gas chromatography with electron capture, insulin by radioimmunoassay and glucose by the enzymatic glucose oxidase method.

Results

Both benzodiazepines induced significant psychotropic effects. The acute insulin responses (AIR) were significantly and negatively correlated with the clonazepam plasma concentrations (r = -0.609, P < 0.05, n = 14). However, the mean AIR was not significantly different between the benzodiazepine-treated subjects and the controls. In addition, the parameters of glucose assimilation were significantly decreased as compared with placebo in the subgroup of 7 subjects with plasma clonazepam concentrations higher than 6.0 ng ml^-1 (median and lower limit of effective therapeutic concentrations): 1.37 ± 0.3 versus 2.84 ± 0.60 × 10^-2min^-1 (P = 0.028) for the coefficient of glucose tolerance (K_g), 2.18 ± 0.29 versus 3.71 ± 0.89 × 10^-4μUml^-1min^-1 (P = 0.018) for insulin sensitivity (S_i) and 1.80 ± 0.39 versus 3.59 ± 0.71 × 10^-2min^-1 (P = 0.028) for glucose effectiveness at basal insulin (S_g). These parameters were not significantly modified when diazepam was administered; plasma levels of this drug however, were below the effective therapeutic concentrations (300 ng ml^-1) from min 15 after the end of the perfusion.

Conclusion

The present results suggest that a benzodiazepine, in particular clonazepam, may alter insulin secretion and insulin sensitivity after a single administration in healthy volunteers.

【 授权许可】

   
2004 Chevassus et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

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