Plasma-Level Response Relationships with Fluoxetine and Zimelidine

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Abstract
Summary: The results of pharmacokinetic studies of two recent 5-HT uptake inhibitors, zimelidine and fluoxetine, have pointed to the inadequacy of opendose rising studies for establishing the most appropriate dose of new antidepressants. High plasma concentrations of the active metabolites, norzimelidine and norfluoxetine, were associated with a poorer therapeutic response in patients suffering from major depression. High drug plasma concentrations are also associated with increased side effects. Large fixed-dose placebo controlled studies with fluoxetine have confirmed the findings of the small pharmacokinetic study that lower doses are more effective. Fixed-dose pharmacokinetic studies are recommended as part of the program to establish the best dose of new antidepressants.

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