I have the following code for the zero order followed by 1st order delayed
absorption of a drug with complex absorption. This code is for a two way
crossover study. The simulation runs okay except that the occ=2 data results
show that OCC2 is not getting sufficient drug into compartment 1.
A portion of the code is below. Has anyone experienced this during a
simulation for a drug with complex absorption and if so how was it
resolved?
$MODEL
COMP=(1);DOSE1
COMP=(2);DOSE2
COMP=(CENTRAL,DEFOBS);CENTRAL,DEFDOSE)
$PK
;IOV INTRAOCCASSION
;IIV INTERSUBJECT
;TRT=TREATMENT (TEST OR REFERENCE)
;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;
;2)PARAMETER KAT1 KAR1 FAST ZERO ORDER MG/H
; KAT2 KAR2 SLOW FIRST ORDER MG/H
;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;
OCC1=0
OCC2=0
;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;
;3)SEQUENCE 1 TREATMENTS 1-2
;SEQ1 3,7,8,11,13,14,18,19,20,22,21,23
;SEQ2 1,2,4,5,6,9,10,12,15,16,17,24
;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;
; OCC1 OCC2
; SEQ1 1 2
; SEQ2 2 1
;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;
IF (TRT.EQ.1.AND.SEQ.EQ.1)OCC1=1
IF (TRT.EQ.2.AND.SEQ.EQ.1)OCC2=1
IF (TRT.EQ.2.AND.SEQ.EQ.2)OCC1=1
IF (TRT.EQ.1.AND.SEQ.EQ.2)OCC2=1
IIV1=ETA(1)
IIV2=ETA(2)
IOV=ETA(3)*OCC1 +ETA(4)*OCC2
KAT1=THETA(1)*EXP(IIV1+IOV)
KAR1=THETA(2)*EXP(IIV1+IOV)
KAT2=THETA(3)*EXP(IIV2+IOV)
KAR2=THETA(4)*EXP(IIV2+IOV)
K13=(KAT1*OCC1 + KAR1*OCC2)
K23=(KAT2*OCC1+KAR2*OCC2)
;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;
;4)PARAMETER F ASSUMING THAT F DOES NOT CHANGE FOR PERIODS
;LIKE KA
;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;
;NO IOV ON LOGITT
LOGITT=THETA(5)
LOGITR=THETA(6)
IIV5=ETA(5)
TVF1T=1/(1+EXP(-LOGITT))
TVF1R=1/(1+EXP(-LOGITR))
F1=TVF1T *EXP(IIV5)*OCC1+ TVF1R *EXP(IIV5)*OCC2
F2=1-F1