RE: Unreasonable VSS estimate

From: "Eyas Abu-Raddad" <raddade@mail.rx.uga.edu> Subject: RE: Unreasonable VSS estimate Date: Tue, 8 May 2001 01:59:54 -0400 All suggestions were valuable, some were more than what I asked for. Thanks for all. The problem was, actually, NOT with the flip flop kinetics. I had a problem obtaining reasonable VSS estimates from intravenous (and oral) data. I mentioned flip-flop lest it had something to do with the poor estimate of VSS, which now I understand it could. The VSS estimates were drastically different from what I obtained from INTRAVENOUS data using the SHAM analysis. I agree with Nick that VSS estimation from oral data needs some assumption about absorption. Although fits with the drastically different VSS were good with regard to prediction of observation, this is not my ultimate goal of modeling. I am studying the pharmacokinetics of enantiomers of a compound after administration of pure enantiomers, and racemate. My basic question is whether there is a difference in PK parameters between the 2 enantiomers, and whether there is interaction between the enantiomers (by allowing enantiomers to have a different value of the parameters of interest, and so for enantiomer or racemate administration, and comparing fits and objective functions for those nested models). As a beginning, I wanted to fit each enantiomer's data alone. For the records, it seems that according to Nick's suggestion, using a mixed residual error model (proportional and additive) stabilized the estimate of VSS to a reasonable value(yet a little different that SHAM value), with all other parameter estimates being acceptable and so were the scatters. :) Thanks, Nick! This was obtained using IV data only. Adding PO data complicated things, obviously because of the higher variability and seemingly erratic absorption. I had to fix disposition parameters to obtain good fits. I would like to follow up with another question in my next email. Regards, Eyas