Empiric distributions [PK / PD]

posted by Helmut Homepage – Vienna, Austria, 2012-03-21 16:18 (3760 d 02:07 ago) – Posting: # 8306
Views: 7,608

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 Cmax 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% Cmax 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)

Cmax/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, Cmax/AUC) and 276 subjects (t75%):

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Interesting, isn’t it?



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