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 2 4 young (age: 22 - 40 years) and 24 elderly (age: 59 - 79 years) healt hy subjects. There were no significant changes in blood pressure, hear t rate, and EGG-parameters in both age groups, and no increase in freq uency of adverse events was observed in the elderly. Following a singl e intravenous infusion of 15 mu g/kg for 1 hour, there were no signifi cant differences in nimodipine pharmacokinetics between young and elde rly volunteers. Oral administration (single dose of 30 mg, 30 mg t.i.d . for 6 days), however, resulted in pronounced differences in AUC and C-max between elderly and young subjects when the same doses were give n. Under steady-state conditions the elderly reached significantly hig her C-max (g . mean/SD: 23.3/1.62 mu g/l) and AUG-values (47.5/1.62 mu gh/l) than the young volunteers (13.5/2.03 mu g/l, and 25.7/1.73 mu gh/l, respectively). The absolute bioavailability was 10.6/1.60% in t he elderly and 5.4/2.11% in young subjects, The observed pharmacokinet ic differences in the study most likely reflect the reduced metabolic clearance of nimodipine in the elderly.