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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dangerous content.
Metabolite inhibition model
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
>
> ++++++++++++++++++++++++++++++++++++++++++
>
> ------------
> This message has been scanned for viruses and
>
> dangerous content.
--
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