$PROB    PD model propofol - Steve's simplified Code

$INPUT ID TIME DV MDV EVID CMT RATE AMT 
V1 V2 V3 CL1 CL2 CL3 KE0C EXPO COBL

$DATA  data.csv

$SUBROUTINE  ADVAN6  TOL=3

$MODEL COMP(CENTRAL,DEFDOSE) COMP(PERI1) COMP(PERI2) COMP(EFFECT) 
COMP(CO2a) COMP(CO2e)

$PK
;estimated parameters
   KEL  = THETA(1)*(1+ETA(1)) 
   HILL = THETA(2)*EXP(ETA(2))
   C50  = THETA(3)*EXP(ETA(3))
   KE0  = THETA(4)*(1+ETA(4))
   REST = THETA(5)*EXP(ETA(5))
S5=1/COBL

$DES

;kinetics
C1 = A(1)/V1
C2 = A(2)/V2
C3 = A(3)/V3
C4 = A(4)/V1
DADT(1) = CL2*C2 + CL3*C3 - C1*(CL1+CL2+CL3)
DADT(2) = CL2*(C1 - C2)
DADT(3) = CL3*(C1 - C3)
DADT(4)=KE0*(A(1)-A(4))
IF (C4.LT.0) THEN
EXIT 1 1
ENDIF

U=(C4/C50)**HILL
EFF= U/(1+U)

;Arterial CO2
DADT(5)=KEL*(1-(1-REST)*EFF-(1-EFF)*A(6)**EXPO*A(5))

;Effect Site CO2
DADT(6)=KE0C*(A(5)-A(6))

$ERROR
YIND=F
Y= F+ERR(1)

$THETA
;KEL 		 X0	EC50		KE0	        REST
(0.05,0.11,0.2) (0.8,1.68,3) (0.5,1.33,3) (0.1,0.268,1) (0.7 FIX)

;      KEL   X0    EC50   KE0   REST
$OMEGA 0.117 0.0453 0.246 0.07885 0 FIX

$SIGMA 8.87

$EST   SIG=3 PRINT=5 MAXEVAL=5000 METH=COND INTER POSTHOC NOABORT

$COV

$TABLE
ID EVID MDV CMT KEL HILL C50 KE0 EXPO KE0C COBL REST
C1 C4 TIME YIND ONEHEADER NOPRINT FILE=RESULTS.PRN