Bioequivalence and Bioavailability Forum

Dear all,

Detlew wrote here:

❝ The whole discussion up to here depends on the assumption of log-normality. If this is a reasonable assumption for measures of fluctuation like PTF or swing is left to you.

Good question. For C_max and AUC there’s a consensus that these metrics are lognormal. See also the empiric distribution of AUCs of methylphenidate in 405 subjects in this presentation which agrees with pharmacokinetic considerations and lead to a multiplicative model (or additive on logtransformed data). Steinijans et al.^* state about MR theophylline:

The choice of the multiplicative model and hence the ratio analysis for the plateu time T75% C_max is motivated by the distribution analysis of the plateau time for the test formulation Euphylong^® in n = 102 healthy subjects and n = 85 patients presenting with obstructive pulmonary diseases. The logarithmic normal distribution was superior to the normal distribution (data on file).
(my emphasis)

C_max/AUC, %PTF, and Swing were also analysed based on logtransformed data without further justification.

I looked at my MPH MR data (10–60 mg, SD/MD; linear PK). Data of 303 subjects (HVD, MRT, C_max/AUC) and 276 subjects (t_75%):













Interesting, isn’t it?

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• Steinjans VW, Sauter R, Diletti E. Shape Analysis in Single- and Multiple-Dose Studies of Modified Release Products. In: Blume HH and KK Midha, editors. Bio-International 2. Stuttgart: medpharm Scientific Pub­li­shers; 1995. p. 193–206.