Re: Setting feeding status as covariate

On Wed, May 23, 2012 at 5:37 PM, Bo Zheng <[email protected]> wrote: > Dear Simbarashe, > > Thanks a lot for your e-mail. > > For this drug (high permeability), the result showed that food effect did > not influence the Bioavailability, it only delayed the Tmax and lowed Cmax. > Therefore, I planned to use delayed absorption model to fit. I thought that > food could slow done the emptying of stomach, and my drug is not a > substrate of transporters known to be affected by meals. > > Your paper is very useful. I actually used the same model to fit. But, it > (even without IOV) was over-parametrized . You had 14 time points, I only > have 6 time points (including time 0). > > Bo > > > > On Wed, May 23, 2012 at 11:14 AM, Simbarashe Peter Zvada < > [email protected]> wrote: > >> Dear Bo >> >> Depending on the use of the drug, say for pain you would prefer meals >> which decrease mean transit time while not compromising >> bioavailability. Testing on Tlag is easier to explain. Why would you >> expect ktr to change due to meal effect? Is your drug a substrate of >> transporters known to be affected by meals? >> >> Given that your model is supporting meal effect on kt or tlag, it is a >> bit unusual that you do not have IOVs. Moreover, crossover study. >> >> Six points sounds reasonable unless you missed absoprtion phase. I >> find it easier to explain to clinicians if you test meal effect on >> bioavailability if higher exposures are desired. >> >> You can refer to other models eg. Effect of four different meal types >> on the population pharmacokinetics of rifapentine in heathy male >> volunteers. By Zvada Simbarashe et al. 2010. >> >> >> All the best, >> Simbarashe Zvada (PhD student) >> University of Cape Town >> >> >> >> On 5/23/12, Bo Zheng <[email protected]> wrote: >> > Hi all, >> > >> > >> > My question is if feeding status can be used as covariate of Kt or TLag >> in >> > delayed absorption model (transit or Tlag model) >> > >> > >> > It is a food effect study (19patients, crossover, no meal, low fat and >> high >> > fat). There are 19 patients x 3 feeding status x 6 time points = 342 >> > observations. The data are not rich enough to run the basic transit or >> Tlag >> > population model, and can not support estimating IOV either. >> > >> > >> > But there are correlations between feeding status (setting no meal=1, >> low >> > fat=2, high fat=3) and individually estimated Kt or Tlag. I found the >> > delayed absorption population models worked if I set feeding status as >> > covariate of Kt or TLag. I also found few published paper using feeding >> > status as covariate. >> > >> > >> > So, I wonder if it is acceptable to add feeding status as covariate of >> Kt >> > or TLag. >> > >> > >> > Thanks in advance, >> > >> > >> > Bo >> > >> >> >> -- >> PhD Student >> Pharmacometrics Group >> Division of Clinical Pharmacology >> Department of Medicine >> University of Cape Town >> Phone: 2773 648 3863 >> mobile: +2721 404 7719 >> > > -- PhD Student Pharmacometrics Group Division of Clinical Pharmacology Department of Medicine University of Cape Town Phone: 2773 648 3863 mobile: +2721 404 7719