THE EFFECT OF MULTIPLE ORAL DOSING OF NIMODIPINE ON GLIBENCLAMIDE PHARMACODYNAMICS AND PHARMACOKINETICS IN ELDERLY PATIENTS WITH TYPE-2 DIABETES-MELLITUS

Possible interactions between the calcium channel blocker nimodipine a nd the hypoglycemic sulphonylurea glibenclamide were investigated in p atients with type-2 diabetes mellitus. These 11 patients had taken the ir individually adjusted antidiabetic treatment unchanged for at least 3 months and showed a satisfactory stabilization of their disease. Th e concomitant administration of nimodipine 30 mg t.i.d. for 6 days did not change glibenclamide pharmacokinetics as compared with the findin gs after glibenclamide monotherapy. The normalized AUC(ss,norm) were 1 1.6 (5.0) kg x h x l(-1) at glibenclamide monotherapy and 12.3 (5.1) k g x h x l(-1) after combined medication, resulting in an AUG-ratio for glibenclamide of 109 (23)%. Mean elimination half-lives were determin ed as 2.7 (0.9) h after glibenclamide alone and 3.6 (1.9) h after nimo dipine 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 /1 after combined treatment). Nimodipine pharmacokinetics under nimodi pine and glibenclamide steady-state conditions were similar to finding s in literature: AUC(ss,norm) 0.10 (0.04) mu g X h x l(-1), C-ss,C-max 20.7 (8.3) mu g X l(-1). Hemodynamics, clinical chemistry and toleran ce did not differ during both treatments. Thus, a clinically relevant drug interaction between nimodipine 30 mg t.i.d. and glibenclamide dur ing long-term treatment can be excluded.