RE: Covariate Models Using Weight

From: "Piotrovskij, Vladimir [JanBe]" <VPIOTROV@janbe.jnj.com> Subject: RE: Covariate Models Using Weight Date: Wed, 17 Nov 1999 11:54:41 +0100 Sorry, Nick, I have no time to read your reviews. I've read a lot about allometry when I did PBPK modelling myself (more than 10 years ago). You say CL is not the same in 10 kg child and in 200 kg rugby player. Sure, but it is another story. I this case the difference should better be described in terms of the age effect which may be different from the body size effect. Or do you really think WT is the only reason why CL in those two individuals differs? Even for adults age and body size can independently affect CL. I give you just one example of the analysis I have done recently. The drug was eliminated via renal and hepatic routes in parallel, and the CL submodel was: TVCL = 9.4+0.072*CLCR+0.034*(AGE-75)+0.050*(WT-67) Note, this was mainly the elderly population (median age is 75), however, there were also a lot of young subjects (but no children) in the data set. Note also the model was developed using formal PK study data and sparse data, but the covariate model was based mainly on formal studies. I attach the scatter plot (MS Word Document) of CL random effects vs covariates. I don't know if you can open this attachment, but believe me, no trend can be seen even using a microscope. *****JENNIFER, PLEASE MAKE THE WORD "MS Word Document" THE LINK TO THE FILE 44.DOC ************** I have a lot of similar examples (unfortunately, not published) where the linear model for CL vs. WT works perfectly. If you work with the industry you do not have opportunity to publish a lot. Best regards, Vladimir ---------------------------------------------------------------------- Vladimir Piotrovsky, Ph.D. Janssen Research Foundation Clinical Pharmacokinetics B-2340 Beerse Belgium Email: vpiotrov@janbe.jnj.com