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.