Re: Problem (bug ?) with RATE and F1 in $PK

From: Pierre Maitre <maitre@cdg.ch> Subject: Re: [NMusers] Problem (bug ?) with RATE and F1 in $PK Date: Fri, 02 Nov 2001 17:16:00 +0100 Leonid Gibiansky a écrit : > > I think this is a feature, not a bug. The motivation (at least how I > interpreted it when I came across this problem) is the following: > bioavailability is treated as some factor outside of the system. F1 affect > the input. You may assume that the tablet (or any other drug form) is > reduced (multiplied) by F1 at time of dosing. So available amount is > NEW_AMT=F1*AMT. This does not affect the rate. This is precisely my point: F1 does not affect the data item RATE, and it should: When you administer a sub-cutaneous infusion, your NONMEM data set needs a AMT data item, and a RATE data item. Both are known data values, they are not estimated values. The duration of the infusion is computed internally by NONMEM (or is it by PREDPP ?) as the ratio AMT/RATE. In this case, the duration is a "computed" data , not an estimated parameter (I know that you can *estimate* the duration with the parameter D1, but this is not my intention here). Introducing the bioavailability parameter F1, will - as you say - multiply AMT by F1 at the time of dosing. The data set hasn't changed (we still use the same data set) , but for NONMEM F1 acts as if AMT were reduced by a factor F1. Now, because F1 does not also scale the data item RATE, the duration of the infusion - as viewed by NONMEM - is now reduced by a factor F1 (remember that duration is computed as AMT/RATE)... and the fit is totally screwed up. ... it's hard to call this a "feature" :-) In brief, I have a known amount of drug, a known rate of administration, a known duration of administration, and I just would like to calculate the bioavailability of a continuous sub-cutaneous infusion with ADVAN4. If I could use a DURATION data item (instead of the RATE data item), this would solve my problem, but there is no such animal in the NONMEM zoo. Moreover, I do not intend to use the D1 parameter and estimate the duration, because duration is a data that was precisely measured. Has anyone had this problem, and how was it solved? Thanks for your help Pierre Maitre -- Dr Pierre-O. Maitre Privat Docent FMH Anesthésiologie FMH Pharmacologie Clinique Cabinet médical / A la Joy CH-1272 Genolier Switzerland