RE: Simultaneous pk model of 2 drugs

From: [email protected] [mailto:[email protected]] Sent: Tuesday, September 06, 2016 7:35 AM To: [email protected]; Penland, Chris Cc: [email protected] Subject: RE: [NMusers] Simultaneous pk model of 2 drugs Hi all, I guess that if both drugs are given to the same person, it makes a lot of sense to perform simultaneous modeling, because of physiology, a lot of parameters will show covariance. The PK of one drug can therefore partially explain the PK of the other one (and vice versa). Cheers, Rob --- Dr. R. ter Heine, hospital pharmacist-clinical pharmacologist Head of Clinical Trials Unit, Dept. of Pharmacy Radboudumc T +31-24-36 16405 F +31-24-36 68755 Van: [email protected]<mailto:[email protected]> [mailto:[email protected]] Namens Pavel Belo Verzonden: dinsdag 6 september 2016 3:04 Aan: Penland, Chris CC: [email protected]<mailto:[email protected]> Onderwerp: RE: [NMusers] Simultaneous pk model of 2 drugs Hello Chris, What is the point of modeling 2 drugs in one NONMEM code? Do the drugs interact? For example, you can have 2 monoclonal antibodies competing for or binding to the same target and/or concentration of one drug changes elimination rate or some other parameters of the other one. If they do not interact, you can model them separately. In some cases, even if they interact you can model them separately using dose of one drug as a covariate for the other one. Regards, Pavel On Fri, Sep 02, 2016 at 01:22 PM, Penland, Chris wrote: Greetings NMusers, Does nonmem have the capacity, unbeknownst to me, for modeling two simultaneous drugs? I would like some suggestions about how to define the dataset and model for a subcutaneous drug and oral drug being administered on different schedules. I would use DVID = 1 and 2 for the two plasma pk observations. I figure this soft of thing had to be dealt with in the past when trying to model dynamic DDIs (vs, just taking one of the drugs as a covariate on the other’s parameters). One approach is to specify the compartments for each to be dosed into then have those feed the central, but I’m curious to see if there is something more subtle in the nonmem syntax. Is there something about EVID, that I don’t know that would help (beyond EVID=1 for dosing) What if you had two oral drugs? Would you treat the two dosing compartments as separate and possibly link them together at the parameter/covariance level? Thanks, Chris Chris Penland, PhD ECD / Quantitative Clinical Pharmacology Waltham, MA USA ________________________________ Confidentiality Notice: This message is private and may contain confidential and proprietary information. If you have received this message in error, please notify us and remove it from your system and note that you must not copy, distribute or take any action in reliance on it. Any unauthorized use or disclosure of the contents of this message is not permitted and may be unlawful. Het Radboudumc staat geregistreerd bij de Kamer van Koophandel in het handelsregister onder nummer 41055629. The Radboud university medical center is listed in the Commercial Register of the Chamber of Commerce under file number 41055629. ________________________________ Confidentiality Notice: This message is private and may contain confidential and proprietary information. If you have received this message in error, please notify us and remove it from your system and note that you must not copy, distribute or take any action in reliance on it. Any unauthorized use or disclosure of the contents of this message is not permitted and may be unlawful.