Hello, Iam trying to understand how did WNL estimate Tmax and Cmax in Library Model 11 when the respective ASCII Code doesnt have any specific formula to calculate both Tmax and Cmax for that model Can any body explain me how do we calculate Tmax and Cmax in 2 Compartment oral model Regards Kaushik
Hello, I have a data for which i have fit 2 comp oral model Lib Model 11 and following are the Model Parameters which i determined V1_F=32; K01=0.12 K10=0.09 K12=0.5 K21=0.75 I am interested to calculate Tmax and Cmax in this Model for which estimated the Tmax and Cmax as 11.579553 and 4.808991 respectively, My question is when Alpha>Ka > Beta How can we determine Tmax and Cmax in such situation I referred Wagner’s (1975) paper on this Journal of Pharmacokinetics and Biopharmaceutics, Vol. 2, No. 6, 1974 in which he suggests a formula for Tmax and Cmax which can be applied only under the follwoing conditions ie Ka> Alpha> Beta Pls suggest me right method Regards Kaushik
Please re-read your calculus textbook. In order to get the maximum of a function you have to be able to access its first and second derivative. The root of the first derivative is the location of an extreme value. If the second derivative at this location is negative the extreme is a maximum. It does not mater how you parametrize a two compartment model (hybrid constant, volumes/rate constants, or clearances) you will find out that you cannot get the derivate(s) in closed form. In other words, Cmax/tmax is not directly accessible for any model other than a one-compartment. Wagner’s method is an approximation. It’s better to use an iterative procedure (like in PHX/WNL) which will give you the values with sufficient precision.
Hello Helmut Probably I should have rephrased my question, when i used those Model parameters, WNL is able to estimate Tmax and Cmax as secondary parameters for Model 11 I wanted to know how WNL is able to calculate these Tmax and Cmax secondary parameters for this Model 11 I have even tried to explore the respective ASCII Model file for Lib Model 11, but i did not find any information (rather forrmula) on this Acc to you WNL iteratively estimates it, can you be little clear on this So thats the reason why i have asked the question
Kaushik, Helmut has read the user guide, if you look at page corresponding to model 11 in the classic code you will see it says that Cmax is only estimated for the compiled model, i.e. if you look at the ASCII output you would not have seen Cmax there (since there is no code to calculate it in the Classic WNL ASCII model). 
I’m really not sure what you’re trying to do, but if you want to learn more about modelling then I think you should start practising with the Phoenix models (and use the NLME examples Guide); if you use the button “set WNL model” then the code for the secondary parameters will be inserted for you and there you can see the formula; Cmax=Aexp(-AlphaTmax)+Bexp(-BetaTmax)+Cexp(-GammaTmax) Please also consider attending a training course, if you contact our Indian office they can let you know when the next public course near Hyderabad is - or perhaps you can arrange an onsite training. Asia Pacific (with the exception of Japan, Korea, China, Taiwan) Mr. Anand Gupta Regional Manager – South Asia Pacific Certara Software India Private, LTD. anand.gupta@certara.com Telephone: +91 984 500 6625 Fax: 351 291 210 209 Simon.
Just to add a clarification that Phoenix nlme model will use numerical differentiation to find at what time Tmax occurs. As Simon suggested try using a WNL mode from within a phoenix model and you can understand how each secondary parameter can be calculated and what code is used.