The influence of age on the pharmacokinetics of nimodipine.
Single and multiple dose pharmacokinetics and absolute bioavailability of the calcium antagonist nimodipine (Nimotop) were investigated in 24 young (age: 22 - 40 years) and 24 elderly (age: 59 - 79 years) healthy subjects. There were no significant changes in blood pressure, heart rate, and ECG-parameters in both age groups, and no increase in frequency of adverse events was observed in the elderly. Following a single intravenous infusion of 15 micrograms/kg for 1 hour, there were no significant differences in nimodipine pharmacokinetics between young and elderly volunteers. Oral administration (single dose of 30 mg, 30 mg t.i.d. for 6 days), however, resulted in pronounced differences in AUC and Cmax between elderly and young subjects when the same doses were given. Under steady-state conditions the elderly reached significantly higher Cmax (g.mean/SD: 23.3/1.62 micrograms/l) and AUC-values (47.5/1.62 micrograms*h/l) than the young volunteers (13.5/2.03 micrograms/l, and 25.7/1.73 micrograms*h/l, respectively). The absolute bioavailability was 10.6/1.60% in the elderly and 5.4/2.11% in young subjects. The observed pharmacokinetic differences in the study most likely reflect the reduced metabolic clearance of nimodipine in the elderly.
Mück
W
W
Institute of Clinical Pharmacology, Pharma Research Center, Bayer AG, Wuppertal, Germany.
Breuel
H P
HP
Kuhlmann
J
J
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D019540:Area Under Curve; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006207:Half-Life; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009553:Nimodipine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D012727:Sex Characteristics
D002121:Calcium Channel Blockers; D009553:Nimodipine