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Re: Metabolite inhibition model

From: Nick Holford <n.holford>
Date: Fri, 19 Sep 2008 19:10:39 +1200

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
n.holford
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
Received on Fri Sep 19 2008 - 03:10:39 EDT

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