Titre du document / Document title

The effect of multiple oral dosing of nimodipine on glibenclamide pharmacodynamics and pharmacokinetics in elderly patients with type-2 diabetes mellitus

Auteur(s) / Author(s)

MÜCK W. ⁽¹⁾ ; HEINE P. R. ; BREUEL H.-P. ; NIKLAUS H. ; HORKULAK J. ; AHR G. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Bayer AG, Pharma Forschungszent., Inst. Klin. Pharmakologie Internationale, 42096 Wuppertal, ALLEMAGNE

Résumé / Abstract

Possible interactions between the calcium channel blocker nimodipine and the hypoglycemic sulphonylurea glibenclamide were investigated in patients with type-2 diabetes mellitus. These 11 patients had taken their individually adjusted antidiabetic treatment unchanged for at least 3 months and showed a satisfactory stabilization of their disease. The concomitant administration of nimodipine 30 mg t.i.d. for 6 days did not change glibenclamide pharmacokinetics as compared with the findings after glibenclamide monotherapy. The normalized AUC_SS,norm were 11.6 (5.0) kg×h×l^-1 at glibenclamide monotherapy and 12.3 (5.1) kg×h×l^-1 after combined medication, resulting in an AUC-ratio for glibenclamide of 109 (23)%. Mean elimination half-lives were determined as 2.7 (0.9) h after glibenclamide alone and 3.6 (1.9) h after nimodipine comedication. There was no evidence of significant alterations in glibenclamide efficiency as seen from glucose and insulin kinetics after the simultaneous administration of glibenclamide and nimodipine (insulin C_max 57.0 (30.8) mU/l after glibenclamide and 64.4 (32.1) mU/l after combined treatment). Nimodipine pharmacokinetics under nimodipine and glibenclamide steady-state conditions were similar to findings in literature: AUC_SS,norm 0,10 (0.04) μg×h×l^-1, C_SS,max 20.7 (8.3) μg×l^-1. Hemodynamics, clinical chemistry and tolerance did not differ during both treatments. Thus, a clinically relevant drug interaction between nimodipine 30 mg t.i.d. and glibenclamide during long-term treatment can be excluded

Revue / Journal Title

International journal of clinical pharmacology and therapeutics   ISSN 0946-1965 

Source / Source

1995, vol. 33, n^o2, pp. 89-94 (22 ref.)

Langue / Language

Anglais

Editeur / Publisher

Dustri, München, ALLEMAGNE  (1994) (Revue)

Mots-clés anglais / English Keywords

Hypoglycemic agent ; Calcium antagonist ; Oral administration ; Non insulin dependent diabetes ; Drug combination ; Drug interaction ; Pharmacokinetics ; Chemotherapy ; Treatment ; Multiple dose ; Elderly ; Sulfonylureas ; Dihydropyridine derivative ; Human ; Endocrinopathy ;

Mots-clés français / French Keywords

Glibenclamide ; Nimodipine ; Hypoglycémiant ; Antagoniste calcium ; Voie orale ; Diabète non insulinodépendant ; Association médicamenteuse ; Interaction médicamenteuse ; Pharmacocinétique ; Chimiothérapie ; Traitement ; Dose répétée ; Vieillard ; Sulfonylurées ; Dihydropyridine dérivé ; Homme ; Endocrinopathie ;

Mots-clés espagnols / Spanish Keywords

Hipoglicemiante ; Antagonista calcio ; Vía oral ; Diabetes no insulinodependiente ; Asociación medicamentosa ; Interacción medicamentosa ; Farmacocinética ; Quimioterapia ; Tratamiento ; Dosis múltiple ; Anciano ; Sulfonilureas ; Dihidropiridine derivado ; Hombre ; Endocrinopatía ;

Localisation / Location

INIST-CNRS, Cote INIST : 15902, 35400005836961.0060