Critical Evaluation of Thioridazine Bioequivalence

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Abstract
The phenothiazines have exhibited a history of problems associated with the bioequivalence of solid oral dosage forms. The more recent availability of chemically equivalent forms of thioridazine has raised new and interesting questions about the appropriateness of generic product interchange, even among brands that have been designated “therapeutically equivalent” by the Food and Drug Administration. The scrutiny that has accompanied the consideration of thioridazine products for inclusion into various state generic substitution formularies has offered an opportunity to examine issues involving bioequivalency in considerable detail. Specific bioequivalency concerns relate to: Correct analysis of drug in biological fluids; the importance of evaluating active metabolites; single-dose vs. multiple-dose crossover studies; appropriate statistical power analysis; the “70/70” rule, and comparison of product variabilities. Examples of problems are cited to illustrate that significant questions still remain about the appropriate factors that should be used to establish bioequivalency.