ETA1 tending to zero in a simple model

Hi, I am currently model building with a neonatal PopPK dataset for a renally eliminated drug and have encountered the following problem: When I add serum creatinine level (SCR) or post-conceptual age (PCA) as a sole covariate, or almost any combination of two covariates, on the clearance model my ETA1 goes to 1.00E-04 as if I had over-parametrised, yet I only have one ETA term on the CL. This situation then triggers the failure of the covariance step due to a parameter estimate being to close to its boundary. What is the likely cause of this and what strategy can I pursue to avoid it? For completeness the relevant excerpts of a typical control file are given (using SCR as the sole covariate in this case): $SUBROUTINE ADVAN1,TRANS2 $PK TVCL=THETA(1)*EXP(THETA(3)*SCR) CL=TVCL*EXP(ETA(1)) TVV=THETA(2) V=TVV*EXP(ETA(2)) SC=V $ERROR Y=F+EPS(1) $EST PRINT=5 METHOD=1 $COVARIANCE Grateful for any help/suggestions/comments offered! All the best, -- Stephen Montgomery School of Pharmacy Queen's University Belfast 97 Lisburn Road Belfast BT9 7BL Tel: (028) 9097 2033