Nick,
You seem to have made at few errors in the NM-TRAN code you sent
yesterday. Perhaps you shouldn't try replying to these kinds of
questions on a Friday night after a couple of glasses of wine!
$INPUT ID TIME DVID DV etc
$SUBROUTINE ADVAN6 TOL=3
$MODEL COMP (LIDO1) COMP (LIDO2) COMP (MEGX)
$PK
;LIDO parameters
V1= THETA(1)*EXP(ETA(1))
CLLIDO=THETA(2)*EXP(ETA(2)) ; Lido clearance in absence of MEGX
V2= THETA(3)*EXP(ETA(3))
Q=THETA(4)*EXP(ETA(4))
;MEGX parameters
KI=THETA(5)*EXP(ETA(5)) ; inhibition constant for MEGX on LIDO clearance
CLMEGX=THETA(6)*EXP(ETA(6))
VMEGX=THETA(7)*EXP(ETA(7))
$DES
DC1=A(1)/V1
DC2=A(2)/V2
DMEGX=A(3)/VMEGX
CL=CLLIDO*(1-DMEGX/(KI+DMEGX)) ;MEGX inhibitory effect on LIDO
clearance. Assumes MEGX can completely inhibit LIDO metabolism.
DADT(1)=Q*DC2−(Q+ CL)*DC1 ;Assumes all LIDO is converted to MEGX
DADT(2)=Q*(DC1−DC2)
DADT(3)=DC1*CL - DMEGX*CLMEGX
$ERROR
CLIDO=A(1)/V1
CMEGX=A(3)/VMEGX
;You need to add DVID data item to your data set to identify which
records are LIDO and which are MEGX observations.
IF (DVID.EQ.1) THEN ; LIDO conc
Y=CLIDO*(1+ERR(1))
ELSE ; MEGX conc
Y=CMEGX*(1+ERR(2))
ENDIF
Best wishes,
Nick
Nick Holford wrote:
Yung-Wei,
If I make the assumption that you have measurements of MEGX as well as
lidoocaine then you might be able to fit the MEGX and LIDO concs at
the same time like this:
$SUBROUTINE ADVAN6 TOL=3
$MODEL COMP (ONE) COMP (TWO)
$PK
V1= THETA(1)*EXP(ETA(1))
CLLIDO=THETA(2)*EXP(ETA(2))
KI=THETA(3)*EXP(ETA(3))
V2= THETA(4)*EXP(ETA(4))
Q2=THETA(5)*EXP(ETA(5))
;add parameters for MEGX here
...
$DES
DC1=A(1)/V1
DC2=A(2)/V2
DMEGX=A(3)/VMEGX
CL=CLLIDO*DMEGX/(KI+DMEGX) ; MEGX effect on LIDO clearance
DADT(1)=Q2*DC2−(Q2+ CL + CLMEGX)*DC1
DADT(2)=Q2*(DC1−DC2)
DADT(3)=DC1*CL2M - DMEGX*CLMEGX
$ERROR
C1=A(1)/V1
CMEGX=A(3)/VMEGX
IF (DVID.EQ.1) THEN ; need to add DVID data item to your data set to
identify which records are LIDO and which are MEGX
Y=C1*(1+ERR(1))
ELSE
Y=CMEGX*(1+ERR(2))
ENDIF
Yung-Wei Hsu wrote:
Dear All,
I am working on lidocaine PK data from 106 patients receiving
infusion for 48 hours. The metabolite (MEGX) will decrease the
clearance of the parent drug (lidocaine). Therefore, I analyzed the
data with nonlinear PK model (ADVAN6 TOL=3). I am wondering whether
there is any metabolite inhibition model to analyze the lidocaine PK.
Any comment or suggestion will be highly appreciated.
Yung-Wei Hsu
Mackay Memorial Hospital
Taipei, Taiwan
+++++++++++++++++
$SUBROUTINE ADVAN6 TOL=3
$MODEL COMP (ONE) COMP (TWO)
$PK
V1= THETA(1)*EXP(ETA(1))
VMAX=THETA(2)*EXP(ETA(2))
KM=THETA(3)*EXP(ETA(3))
V2= THETA(4)*EXP(ETA(4))
Q2=THETA(5)*EXP(ETA(5))
$DES
DC1=A(1)/V1
DC2=A(2)/V2
CL=VMAX*DC1/(KM+DC1)
DADT(1)=Q2*DC2−(Q2+ CL)*DC1
DADT(2)=Q2*(DC1−DC2)
$ERROR
C1=A(1)/V1
Y=C1*(1+ERR(1))
IPRED=Y
++++++++++++++++++++++++++++++++++++++++++
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--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
[EMAIL PROTECTED] tel:+64(9)923-6730 fax:+64(9)373-7090
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
