RE: covariates

From: "Ying Hong" yinghong@pharm.usyd.edu.au Subject: RE: [NMusers] covariates Date: Fri, September 17, 2004 10:50 pm Hello, Nick, Leonid I did try the allometric scaling law for each PK parameter (CL, V1, Q, V2) one by one in the basic model. Unfortunately, the results are either Minimization terminated or insignificant change of OFV. It seems that allometric scaling model doesn't fit to my study data. Perhaps, the formulation of this study drug, liposome, may modify the disposition of encapsulated drug which can not be explained by allometric scaling model. I also tried the covariate equation like that: TVP = THETA(1) * (1 + THETA(2) * (COV - median(COV)) ; P is the PK parameter ;COV is the covariate However, error message shows that P is negative (don't know why?). So, I am back to the allometric modelling again, and this time I replace 0.75 or 1 with THETA(5) like that: TVP = THETA(1) * (WT / 21) ** THETA(5) ; 21 is the median of WT in the study patient cohort ; the minimum and maximum limit of THETA(5) was given in the THETA block The results seems to be OK since OFV decreased significantly and CV% of CL and V1 also decreased. Is it proper to do in this way by letting NONMEM to find the THETA(5) estimate? If yes, Can I fix this THETA(5) to the final estimate when running the next level by incorporating more covariates? Kind Regards, Renee