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document
Analysis of multiple-dose bioequivalence studies . In multiple-dose bioequivalence studies , it is possible at steady state to take repeated measurements of pharmacokinetic variables , such as area under the curve ( AUC ) and the maximum concentration ( CMAX ) of the blood concentration-time profile , within each period of a crossover design . We develop a bivariate random effects model for such a situation in a 2 x 2 crossover design using the natural log scale for AUC and CMAX that assumes no differential carryover effects and includes components for inter- and intrasubject variability with respect to both formulations . We derive the uniformly minimum variance unbiased estimators , which also happen to be restricted maximum likelihood estimators , and we provide a sample size formula .
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Intervention_Pharmacological
multiple-dose bioequivalence studies
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Outcome_Other
pharmacokinetic variables
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Outcome_Other
area under the curve ( AUC )
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Outcome_Other
maximum concentration ( CMAX )
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Outcome_Other
bivariate random effects model
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Outcome_Other
natural log scale for AUC and CMAX
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Participant_Condition
multiple-dose bioequivalence studies