Age effect on Clearance

Dear nmusers, I am getting funny results when i add age as a covariate on oral clearance: The OF decreases by 16 points, but : BSV on CL increases from 35% to 37% BSV on V decreases from 49% to 47% Intra-Individual variability decreases from 41% to 38% And the most important is that the age had a positive effect on CL Where CL INCREASED with age (THETA2 = -0.37 ). Age is not correlated to other covariates and remained significant in the final model together with the body weight. I also tried several ways to test the effect of age , but NONMEM didn't converge. I also had funny results when i tried FOCE-I method, because i got a very small variability on oral CL (0.7%) though i had much lower OF (-55 points) and the Covariance step failed. I used the following: $SUB ADVAN2 TRANS2 $PK MAGE = 40 ; Median age FAGE = (AGE-MAGE)/MAGE ; Fractional effect of age TVCL = THETA(1)* (1- THETA(2)*FAGE) CL = TVCL * EXP (ETA(1)) V = THETA(3)* EXP (ETA(2)) KA = THETA(4) F1 = THETA(5) S2=V/1000 $THETA (0,10)(0.5)(0,100)(0,0.6)(1 FIX) $OMEGA 0.5 0.5 $ERROR Y=F*EXP(ERR(1)) IPRED=F IRES=DV-IPRED W=F; if err prop W=F else W=1 IWRES=IRES/W $SIGMA 0.5 $ESTIMATION SIGDIGITS=3 METHOD=1 MAXEVAL=9999 NOABORT POSTHOC PRINT=1 $TABLE UNCONDITIONAL ID TIME AMT CL V KA DV PRED IPRED IRES RES WRES IWRES AGE SEX BW HGT ETA1 ETA2 EVID NOPRINT ONEHEADER FILE=run08.table.txt Any suggestions on how to handle these results?? Thank you in advance for your help Mona