Re: T matrix

From:Nick Holford Subject:Re: [NMusers] T matrix Date:Fri, March 8, 2002 4:36 pm > From: > "Emily" > First, I'd like to thank Nick. After gave smaller Vm and bigger k12, I still got > the same error message. What esle > can I do ? You should consider using ADVAN10 which is a special case for the one compartment Michaelis-Menten elimination model. This may be more numerically stable than ADVAN6 (or 8 or 9) because it does not rely on numerical integration to solve the PK model. Have you looked at graphs of time vs obs and individual (posthoc) predictions of conc? You need to be sure you have a good fit before worrying about the small print standard error issues. You should understand that the SEs provided by NONMEM are not worth much. If you want to use them as measure of the confidence interval for your parameters then they rely on at least two untenable asssumptions 1) you have an infinite amount of data 2) the confidence intervals are symmetrical around the parameter estimate. Alternative empirical methods e.g. bootstrap or log likelihood profile are better way of understanding the confidence you have in your parameters. Its unlikely you have a stiff system especially if you now have more realistic estimates of Vmax and Ka. You can easily try using ADVAN9 (just change ADVAN6 to ADVAN9 and re-run). Sometimes ADVAN9 is more robust. I have not had much luck with ADVAN8 which is designed for systems that really are stiff ie. different rate constants in the model vary by several orders of magnitude e.g having an absorption half-life of a few minutes and an elimination half life of several days. Nick -- Nick Holford, Divn Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/