RE: Unable to achieve Cmax

Dear Anuja, First of all, having 1-compartment distribution for some subjects and 2-compartment distribution for others rarely makes any sense. If this is what you are using I would really suggest to get rid of that. Below you will find an answer to a similar question regarding “double peak absorption” from some years back. This might be a useful starting point for you. http://cognigencorp.com/nonmem/current/2010-October/2054.html The proposed approach in the above answer can be modified in many ways e.g. - Add 2-N transit compartments for one or two of the absorption paths - Add a zero-order absorption for one or two of the absorption paths (see NONMEM user guide for implementation by setting RATE==-1 or RATE==-2) I would propose that you investigate different permutation of this until you achieve what can be described as an adequate description of the absorption. It can always get better but be satisfied with you have something that seems “good enough”. Notice that with modelling of only oral data it can be difficult to fully separate absorption and disposition processes (distribution and elimination). For that reason it is important to look for other information on the disposition PK for the drug to make sure that the model is adequately parameterized with regards to distribution (e.g. 1/2/3 distribution compartments) and elimination (e.g. linear v.s. saturable elimination). This information can come from the literature and/or i.v. data on file. Prior information about the appropriate model structure should be used but it may also be necessary to include prior information about the estimates for parameters with low identifiability given the design of the experiment (check $PRIOR in the NONMEM used guide). Best regards, Martin Bergstrand, Ph.D. Senior Consultant Pharmetheus AB +46(0)709 994 396 [email protected] www.pharmetheus.com +46(0)18 513 328 U-A Science Park, Dag Hammarskjölds v. 52b 752 37 Uppsala, Sweden *This communication is confidential and is only intended for the use of the individual or entity to which it is directed. It may contain information that is privileged and exempt from disclosure under applicable law. If you are not the intended recipient please notify us immediately. Please do not copy it or disclose its contents to any other person.* *From:* [email protected] [mailto:[email protected]] *On Behalf Of *Anuja Dhas *Sent:* Thursday, December 07, 2017 6:48 AM *To:* [email protected] *Subject:* [NMusers] Unable to achieve Cmax Dear All, I am a Beginner for NONMEM. I am having a dataset of oral BE study. The Drug is BCS III and tmax is 0.5-2hrs. I have observed lag time and double peak; but I am not assure it is double peak or sampling error. I have used ALAG in the control file to deal with lag time. The half of the subjects are following 1 compartmental absorption and the rest are following 2 compartmental absorption. So I separately modeling each compartment. Is it right method?? Should I use transit model? The elimination phase is captured well; but I am unable to achieve Maximum Concentration. The CWRES vs. Time & CWRES vs.PRED plots clearly indicates bias at high concentration. Please suggest me some needful actions to deal with these problems. *Best Regards* *Anuja* ------------------------------ "Legally privileged confidential information and subject to "Disclaimer". http://www.cipla.com/Home/Other/Disclaimer.aspx