Zimelidine to geriatric patients: a pharmacokinetic and clinical study.

To evaluate the clinical efficacy, tolerance and pharmacokinetic properties of zimelidine in elderly people, twelve hospitalized depressed patients with a mean age of 80 years were included in a clinical trial. Zimelidine was administered twice daily at a dose of 50 mg during the first week, 75 mg during the second week and 100 mg during the third to sixty week. The patients also received a single oral test dose of 75 mg of zimelidine during an initial placebo week. All patients that completed the study improved according to the rating scales used. The drug was well tolerated, and adverse reactions were few and of mild or moderate severity. No influence of clinical importance was noted on hematology, liver and kidney functions, ECG, blood pressure or pulse rate. The mean elimination half-lives of zimelidine and norzimelidine were found to be 15 h and 35 h, respectively, which were longer than the half-lives earlier obtained in younger patients. The blood levels (AUC) in the geriatric patients were about twice those obtained earlier in healthy volunteers. The AUC values for both zimelidine and norzimelidine increased in close proportion to the increase in dose and, thus, the pharmacokinetics of zimelidine was apparently not dose-dependent in the dose interval used. The results obtained may indicate a reduction in the rate of metabolism for zimelidine in the elderly, possibly combined with increased total bioavailability of the drug. A reduction of the regular zimelidine dose may be recommended in the treatment of elderly patients.