Zimeldine to geriatric patients in once daily dosage. A pharmacokinetic and clinical study.
The therapeutic efficacy, tolerability and pharmacokinetics of zimeldine in elderly depressed patients were evaluated after administration of different doses of the drug in once daily evening doses. The doses of zimeldine were 100 mg during the first 2 weeks, 150 mg during the next 2 weeks and 200 mg during the last 2 weeks. Nine of the 11 patients (mean age 78 years) included in the study completed the 6-week treatment period, and all nine improved according to the Hamilton depression rating scale. The drug was well tolerated and the side effects were few and mild. No influence of clinical importance was noted in haematology, liver and kidney functions, EEG, blood pressure or pulse rate. Steady-state plasma concentrations of zimeldine, and its active metabolite norzimeldine, were achieved in most cases after 1 week of treatment in each dose regimen. The plasma concentrations increased linearly with the increase in dose. The maximal interindividual variations in plasma concentrations were 8-fold for zimeldine and 3-fold for norzimeldine . The plasma levels of both zimeldine and norzimeldine were higher in the elderly than reported earlier in younger patients. The ratio of norzimeldine/zimeldine concentrations was reduced in the elderly, indicating a reduction of the metabolic capacity. The results suggest that zimeldine can be administered in a once daily dosage regimen to elderly patients, but they should be given a lower dose than younger patients.