RE: Emax model

Hi Marie, I would like to state, in my view, that the terminology "direct" is not based on a clear understanding of PKPD. The terminology of direct and indirect should be avoided. These terms might be translated into immediate and delayed effects but it's better to use more precise terms to describe what you want to use your PKPD model to describe. In real biology there is no such thing as an immediate effect. All drug effects must have some delay between changes in plasma unbound concentration and the development of the effect associated with that concentration. These delays may include distribution from plasma to the effect site, binding of the drug once it has reached its effect site to its receptor and transduction into a stimulus leading to the effect, turnover of physiological mediators that are change such things as the input or elimination of physiological mediators that lead to the observed effect. I'd be happy to provide NONMEM code for an immediate effect with an Emax model. But you should think carefully before using it to describe real observed effects which must be delayed in relation to the concentrations used in PK models. Best wishes, Nick -- Nick Holford, Professor Emeritus Clinical Pharmacology, MBChB, FRACP mobile: NZ+64(21) 46 23 53 ; FR+33(6) 62 32 46 72 email: [email protected]<mailto:[email protected]> web: http://holford.fmhs.auckland.ac.nz/