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 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