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 on 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 AUCss,norm were 11.6 (5.0) kg x h x 1(-1) at glibenclamide monotherapy and 12.3 (5.1) kg x h x 1(-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 Cmax, 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: AUCss,norm 0.10 (0.04) microgram x h x 1(-1), Css,max 20.7 (8.3) microgram x 1(-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.
Mück
W
W
Institut für Klinische Pharmacologie International, Pharma Forschungszentrum, Bayer AG, Wuppertal, Germany.
Heine
P R
PR
Breuel
H P
HP
Niklaus
H
H
Horkulak
J
J
Ahr
G
G
D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D005905:Glyburide / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006207:Half-Life; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009553:Nimodipine / Q000008:administration & dosage / Q000494:pharmacology*; D011674:Pulse / Q000187:drug effects
D001786:Blood Glucose; D007328:Insulin; D009553:Nimodipine; D005905:Glyburide