$PROBLEM    2 compartment fitting
  $INPUT       ID TIME AMT DV WTKG GENDER AGE {D1LAG[1]}
  $DATA      {data_dir}/datalarge.csv IGNORE=@
            
  $SUBROUTINE {ADVAN[1]} ;; ADVAN2, ADVAN4, ADVAN12
  $PK      
  CWTKGONE = WTKG/70  ;; CENTERED ON ONE
  CWTKGZERO = WTKG-70  ;; CENTERED ON ZERO
  CAGE = AGE/40 
  TVV2=THETA(2){V2~WT[1]} {V2~GENDER[1]} ;; optional covariates effects of WT and Gender
  V2=TVV2*EXP(ETA(2)) 
  TVCL= THETA(1) {CL~WT[1]}  {CL~AGE[1]} ;; optional covariates effects of WT and AGE
  CL=TVCL*EXP(ETA(1)) 
  K=CL/V2 
  {ADVAN[2]}         ;; for K23,K32,K24,K42 needed?
  {D1LAG[2]}         ;; include D1 and lag, with diag or block OMEGA
   
  TVKA=THETA(3) 
  KA=TVKA  {KAETA[1]}  
  S2 	= V2/1000 
  $ERROR     
  REP = IREP      
  IPRED =F  
  IOBS = F {RESERR[1]}
  Y=IOBS
  $THETA  ;; must be one THETA per line.
  (0.001,100)	; THETA(1) CL UNITS =  L/HR
  (0.001,500) 	; THETA(2) V  UNITS = L
  (0.001,2) 	; THETA(3) KA UNITS = 1/HR  

  {ADVAN[3]}  ;; are initial estimates for K23,K32,K24,K42 needed?
  {V2~WT[2]}   ;;; is initial estimate for Volume a function of weight needed?
  {V2~GENDER[2]}   ;;; is initial estimate for Volume a function of gender needed?
  {CL~WT[2]} 
  {CL~AGE[2]} 
  {D1LAG[3]}
  $OMEGA   ;; must be one ETA/line
    0.2  		; ETA(1) CLEARANCE
  $OMEGA 
    0.2 	; ETA(2) VOLUME
  ;; optional $OMEGA blocks
  ;; optional initial estimates for ETA on KA
  {KAETA[2]}
   
  ;; optional initial estimates for ETA on D1 and ALAG1
  {D1LAG[4]}
  $SIGMA   

  {RESERR[2]}   ;; additive or proportional or combined
  $EST METHOD=COND INTER MAX = 9999 MSFO=MSF1 
  $COV UNCOND PRINT=E