Linear VS LTBS

Hi, while data fitting using NONMEM on a regular PK data set and its log transformed version I made the following observations - PK parameters (thetas) were generally similar between regular and when using LTBS. -ETA on CL was similar -ETA on Vc was different between the two runs. - Sigma was higher in LTBS (51%) than linear (33%) Now using LTBS, I would have expected to see the ETAs unchanged or actually decrease and accordingly I observed that the eta values decreased showing less BSV. However the %RSE for ETA on VC changed from 40% (linear) to 350% (LTBS) and further the lower 95% CI bound has a negative number for ETA on Vc (-0.087). What would be the explanation behind the above observations regarding increased %RSE using LTBS and a negative lower bound for ETA on Vc? Can a negative lower bound in ETA be considered as zero? Also why would the residual vriability increase when using LTBS? Please note that the PK is multiexponential (may be this is responsible). Thanks. Neil -- Indranil Bhattacharya