$PROBLEM    2 compartment fitting
$INPUT       ID TIME AMT {D1LAG[1]} DV MDV EVID WT AGE SEX BUN SCR OCC CRCL COV1 COV2

$DATA      {data_dir}/dataWithPeriod.csv IGNORE=@
           
$SUBROUTINE {ADVAN[1]} 
$PK      
  CWTKGONE = WT/81  ;; WEIGHT CENTERED ON ONE
  CWTKGZERO = WT-81 ;; WEIGHT CENTERED ON ZERO
  CAGE = AGE/60     ;; AGE CENTERED ON ONE
  CCRCL = CRCL/85.6 ;; CRCL CENTERD ON ONE
  CCOV1 = COV1-15.4 ;; COVARIATE 1 CENTERED ON ZERO
  {IOVV[1]}  
  TVV2=THETA(1) {V2~WT[1]} {V2~SEX[1]} {V2~AGE[1]} {V2~COV2[1]}  *EXP(IOVV)
  V2=TVV2*EXP(ETA(2))   
  {IOVCL[1]}
  TVCL= {INITCL[1]} {CL~WT[1]} {CL~AGE[1]} {CL~CRCL[1]} {CL~COV1[1]} *EXP(IOVCL)
  CL=TVCL*EXP(ETA(1)) 
   
  K=CL/V2      
  {ADVAN[2]}  
  {D1LAG[2]}    
  TVKA=THETA(2) 
  KA=TVKA  {KAETA[1]}    
  S2 = V2 
$ERROR     	
 REP = IREP      
 IPRED =F  
 IOBS = F {RESERR[1]}
 Y=IOBS
$THETA      
 (0.001,100) 	; THETA(1) V  UNITS = L
 (0.001, 10) 	; THETA(2) KA UNITS = 1/HR    
 {INITCL[2]}	; THETA(INITCL) CL UNITS =  L/HR
 {ADVAN[3]}   
 {V2~WT[2]}   
 {V2~SEX[2]}   
 {V2~AGE[2]} 
 {V2~COV2[2]}
 {CL~WT[2]} 
 {CL~AGE[2]} 
 {CL~CRCL[2]}
 {CL~COV1[2]}
 {D1LAG[3]}
$OMEGA    
 0.1  		; ETA(1) CLEARANCE 
 0.4  		; ETA(2) VOLUME  
{KAETA[2]}  
{D1LAG[4]} 
{IOVCL[2]}
{IOVV[2]}
$SIGMA   
 {RESERR[2]}

$EST METHOD=COND INTER MAX = 9999 MSFO=MSF1 PRINT = 10
$COV UNCOND PRINT=E  PRECOND=1 PRECONDS=TOS  MATRIX = R