PHARMACOKINETICS OF OXIRACETAM IN ELDERLY PATIENTS AFTER 800 MG ORAL DOSES, COMPARISON WITH NONGERIATRIC HEALTHY-SUBJECTS

The pharmacokinetics of oxiracetam have been studied in eighteen elderly patients and in six healthy non-geriatric adults. A 800 mg single oral dose was administered in the morning of the first day and repeatedly, every 12 h, from day 2 evening to day 10 morning, to the elderly patients. The healthy non-geriatric adults were given a 800 mg single oral dose of oxiracetam. In healthy non-geriatric subjects after a single oral administration of 800 mg, the normalized plasma levels of oxiracetam for 1 mg/kg dose were similar to those already recorded after a 2000 mg single dose of oxiracetam. Therefore, there was no tendency towards non-linear pharmacokinetics of oxiracetam between 800 and 2000 mg single doses in healthy subjects. After the single oral dose, the mean area under the plasma concentration-time curve of oxiracetam in elderly patients was increased by a factor of two as compared to that observed in non-geriatric healthy subjects whereas the maximum concentration (Cmax) was almost not modified and slightly delayed. This can be explained by a slower absorption and elimination in the elderly patients. The highest oxiracetam levels were predominantly recorded in the oldest patients. The slower elimination (mean T1/2=12.3 h in elderly and 7.7 h in healthy subjects) could be attributed to a physiological decrease of the renal function. The volume of distribution was not significantly modified in the elderly patients. No modification of the pharmacokinetics of oxiracetam was recorded after repeated administration in elderly patients as shown by the good agreement between the oxiracetam steady-state level in plasma predicted from the concentrations after the first dose and the concentrations actually measured after repeated dosing. The prediction indicates that the steady-state would be reached 48 h after the first dose when 800 mg of the drug was given twice daily. The mean Cmax was 140 μmol/l after the first dose and 196 μmol/l after the last dose. Since the dosing schedules recommended for oxiracetam have been mostly established on the basis of the results in old patients, a reduction of doses does not seem suitable in elderly patients, with the exception of patients with impaired renal function. © 1990 Springer-Verlag.