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Background: For many racemic drugs, bioequivalence assessment based on isomer-nonspecific assays is appropriate because enantiomeric area under the concentration-time curve (AUC) exposure ratios are close to unity. Use of nonspecific methods in cases in which the ratio is substantially greater or less than 1, however, may obscure real therapeutic differences among formulations, especially if the enantiomers exhibit differing pharmacological potencies. Objective: To examine the influence of absorption rate on etodolac bioequivalence as measured by total [(R,S)-] and (S)-etodolac. Design: Single dose, 3-period, crossover, pharmacokinetic study in 24 healthy volunteers in which the administration rate of etodolac was varied. Methods: Participants received etodolac 400mg in solution, given as a single dose over 1 minute or as divided doses over 30 and 90 minutes. Unresolved and enantiomer concentrations of etodolac were measured by a validated HPLC assay. The enantiomer ratio was similarly measured by HPLC. Results: Bioequivalence parameters derived for both unresolved and (S)etodolac indicate that peak plasma drug concentration (C[sub max]) was not bioequivalent. By delaying absorption, bioequivalence was lost. Conclusions: Collectively, these data demonstrate that bioequivalence between 2 products of etodolac based on enantiomerically nonspecific criteria alone may not generalise to the pharmacologically relevant (S)-enantiomer. This suggests that enantiospecific assays are necessary for bioequivalence assessments. [ABSTRACT FROM AUTHOR]