$PROBLEM    GENTA-ONCO JULY 1996
$INPUT      ID TIME AMT RATE DUR DV MDV EVID AGE SEX WT HT IBW CR ACR
            CLC ACLC ALB WCC
$DATA      Simulated_gentamicin_pk.dta IGNORE=@
$SUBROUTINE ADVAN3 TRANS4
$PK        BSA=71.84*(WT**0.425)*(HT**0.725)
          BSA=BSA/10000
          HT1=HT/100
          BMI=WT/HT1**2
      IF(NEWIND.NE.2) BCLC = CLC
         DCLC = CLC-BCLC
      IF(NEWIND.NE.2) BBSA = BSA

          TVCL=THETA(1)*(1 + THETA(5)*(BCLC-81)+ THETA(7)*DCLC)
          TVV1=THETA(2)*BBSA*(ALB/34)**THETA(6)
          TVQ=THETA(3)
          TVV2=THETA(4)
          CL=TVCL*EXP(ETA(1))
          V1=TVV1
          Q=TVQ*EXP(ETA(2))
          V2=TVV2
          S1=V1
$ERROR    Y=F*EXP(ERR(1))+ERR(2)
         IPRED=F
         IRES=DV-IPRED
$THETA  (0,4.1) ; CL
$THETA  (1,8.63) ; V1
$THETA  (0,1.21) ; Q
$THETA  (0,8.12) ; V2
$THETA  (-0.01,0.00982,0.016) ; BCLC
$THETA  -0.409 ; ALB
$THETA  (0,0.00683) ; DCLC
$OMEGA  0.0465 ; CL
$OMEGA  0.376 ; Q
$SIGMA  0.0297 ; E1
$SIGMA  0.0486 ; E2
$ESTIMATION MAXEVALS=0 SIG=3 PRINT=10 METHOD=1 INTER
;$COVARIANCE