Emax model

Dear NM users, Hope my message finds you well, Can anyone share NM control streams for a direct Emax PK/PD model? Thank you in advance for your help Marie Marie RAJERISON PharmD PhD Pharmacometrician e-mail: [email protected]<mailto:[email protected]> 128 rue de la Boetie 75008 Paris France [cid:[email protected]]

Dear Marie, There are basically two options: 1. Develop a sequential PK/PD model. First you develop a PK model and you read out the individual predictions for concentrations (IPREDs). Then, using the $PRED subroutine in NONMEM in a new run you can fit an EMAX equation to your PD as dependent value and the IPREDs as independent value. 2. Alternatively, you can develop a simultaneous PK/PD model. You then observe the PK and PD in the same compartment using two separate lines in your dataset, with a column with a flag whether an observation is a PK or PD observation. In the $ERROR block of your model you use two different equations for your residual error where you let your PD error function depend on the individual prediction for concentration in the central compartment. A hybrid method would be first to develop a PK model, fix the THETA/OMEGA/SIGMA for PK and add the PD model to this PK model, using the error block to describe the relationship. Sincerely, Rob Van: [email protected] <[email protected]> namens Marie Rajerison <[email protected]> Datum: woensdag, 9 oktober 2024 om 14:31 Aan: [email protected] <[email protected]> Onderwerp: [NMusers] Emax model Dear NM users, Hope my message finds you well, Can anyone share NM control streams for a direct Emax PK/PD model? Thank you in advance for your help Marie Marie RAJERISON PharmD PhD Pharmacometrician e-mail: [email protected]<mailto:[email protected]> 128 rue de la Boetie 75008 Paris France [cid:[email protected]] De informatie in dit bericht is uitsluitend bestemd voor de geadresseerde. Aan dit bericht en de bijlagen kunnen geen rechten worden ontleend. Heeft u deze e-mail onbedoeld ontvangen? Dan verzoeken wij u het te vernietigen en de afzender te informeren. Openbaar maken, kopi?ren en verspreiden van deze e-mail of informatie uit deze e-mail is alleen toegestaan met voorafgaande schriftelijke toestemming van de afzender. Het Radboudumc staat geregistreerd bij de Kamer van Koophandel in het handelsregister onder nummer 80262783. The content of this message is intended solely for the addressee. No rights can be derived from this message or its attachments. If you are not the intended recipient, we kindly request you to delete the message and inform the sender. It is strictly prohibited to disclose, copy or distribute this email or the information inside it, without a written consent from the sender. Radboud university medical center is registered with the Dutch Chamber of Commerce trade register with number 80262783.

Hi Marie, You can try this GUI to generate this NONMEM code: https://sbihorel.shinyapps.io/pmxcode/ Best Sebastien Bihorel

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/