title: Logarithmic transformation in bioequivalence: application with two formulations of perphenazine.
abstract: 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.
authors.affiliation: College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.
authors.forename: K K
authors.initials: KK
authors.lastname: Midha
authors.forename: E D
authors.initials: ED
authors.lastname: Ormsby
authors.forename: J W
authors.initials: JW
authors.lastname: Hubbard
authors.forename: G
authors.initials: G
authors.lastname: McKay
authors.forename: E M
authors.initials: EM
authors.lastname: Hawes
authors.forename: L
authors.initials: L
authors.lastname: Gavalas
authors.forename: I J
authors.initials: IJ
authors.lastname: McGilveray
mesh_terms: D000293:Adolescent; D000328:Adult; D006801:Humans; D008297:Male; D008433:Mathematics; D008875:Middle Aged; D008954:Models, Biological; D010546:Perphenazine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011863:Radioimmunoassay; D013810:Therapeutic Equivalency
chemical_list: D010546:Perphenazine