Empiric distributions [PK / PD]

posted by Helmut Homepage – Vienna, Austria, 2012-03-21 17:18 (4475 d 00:49 ago) – Posting: # 8306
Views: 8,812

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%):





Interesting, isn’t it?

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

UA Flag
 Admin contact
23,059 posts in 4,841 threads, 1,665 registered users;
44 visitors (0 registered, 44 guests [including 9 identified bots]).
Forum time: 19:07 CEST (Europe/Vienna)

[…] an inappropriate study design is incapable of answering
a research question, no matter how careful the subsequent
methodology, conduct, analysis, and interpretation:
Flawless execution of a flawed design achieves nothing worthwhile.    J. Rick Turner

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz