Logarithmic transformation in bioequivalence: application with two formulations of perphenazine

The rationale for using the logarithmic transformation on concentration-dependent pharmacokinetic parameters a priori is presented. This rationale is based on theoretical pharmacokinetic and statistical grounds, but is also applicable to the practice of physicians in dealing with variations of drug...

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Bibliographic Details
Published inJournal of pharmaceutical sciences Vol. 82; no. 2; p. 138
Main Authors Midha, K K, Ormsby, E D, Hubbard, J W, McKay, G, Hawes, E M, Gavalas, L, McGilveray, I J
Format Journal Article
LanguageEnglish
Published United States 01.02.1993
Subjects
Adolescent
Adult
Humans
Male
Mathematics
Middle Aged
Models, Biological
Perphenazine - administration & dosage
Perphenazine - blood
Perphenazine - pharmacokinetics
Radioimmunoassay
Therapeutic Equivalency
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Summary:The rationale for using the logarithmic transformation on concentration-dependent pharmacokinetic parameters a priori is presented. This rationale is based on theoretical pharmacokinetic and statistical grounds, but is also applicable to the practice of physicians in dealing with variations of drug treatment within and between patients. The implications of the transformation on data analysis, specifically analysis of variance, and estimation and inference from the analysis as it pertains to bioequivalence decisions are explored. Implementation of the transformation is shown, with an example of two perphenazine formulations in a single-dose crossover study. It is concluded that the transformation has to be accepted on theoretical grounds because sample sizes are too small in bioequivalence studies and too susceptible to extreme values to state with any certainty the actual distribution of pharmacokinetic parameters or their differences within a subject.
ISSN:0022-3549
DOI:10.1002/jps.2600820205