Re: Fitting 2 compartment first-order input PK/PD model.

Date: Tue, 14 Sep 1999 09:57:35 -0400 (EDT) From: Jogarao Gobburu 301-594-5661 FAX 301-480-8329 <GOBBURUJ@cder.fda.gov> Subject: Re: Fitting 2 compartment first-order input PK/PD model. Hello, 1. Firstly, I would suggest that you parameterize your PK model using clearances and volumes of distribution. This way, you can interpret the inter-individual variability better. 2. After you finalize your PK model, try to simulate the concentration first to check whether the PK coding in your PD model is correct. Output Cp=A(2)/S2. 3. It may be a good idea to output ONEHEADER in your $TABLE record, for easy identification. 4. You should have a k20 for the elimination of drug from the central compartment. 5. The assumption when using link model is that negligible amount of drug enters the effect site, hence k24 = 0.001*k20 may be more meaningful. 6. Generally, effects of drugs on QT may be quite instantaneous. You might want to check if you need a distrbutional delay model in the first place. Hope this helps ! Regards, Joga Gobburu Pharmacometrics, CDER, FDA.