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I am wondering if anyone at the pharmpk group has the ASCII code for a
2 compartment model with MM elimination within the WInNonlin program.
I am trying to write the ASCII code for the model and having some
difficulty.
I would appreciate any suggestion from any group members.
Thank you very much
Eddie Kwan at UBC
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The following message was posted to: PharmPK
Eddie,
You could try this (untested) code. Note the dose is hard coded. Its up
to you to change this to something more appropriate.
MODEL
remark ******************************************************
remark Developer: Nick Holford
remark Model Date: 05-13-2003
remark Model: first order absortpion, 2 compartment dispostion, mixed
order elimination
remark Single dose. Dose amount is hard coded
remark ******************************************************
remark
remark - define model-specific commands
COMMANDS
NFUNCTIONS 1
NDERIVATIVES 3
NPARAMETERS 6
PNAMES 'Vmax', 'Km', 'V1', 'V2', 'CLic', 'Tabs'
END
remark - define temporary variables
TEMPORARY
remark Define the dose in whatever way suits you e.g.
dose=100
ka=dlog(2)/tabs
END
remark - define differential equations starting values
START
Z(1) = Dose
Z(2) = 0
Z(3) = 0
END
remark - define differential equations
DIFFERENTIAL
RateIn=ka*Z(2)
C1=Z(2)/V1
C2=Z(3)/V2
CL=Vmax/(Km+C1)
DZ(1) = -RateIn
DZ(2) = RateIn + CLic*C2 - (CLic+CL)*C1
DZ(3) = CLic*(C1-C2)
END
remark - define algebraic functions
FUNCTION 1
F= Z(2)/V1
END
remark - define any secondary parameters
remark - end of model
EOM
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
email:n.holford.-a-.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
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The following message was posted to: PharmPK
Eddie,
the following model works fine for drugs like GHB and ethanol.
CLd is the intercompartmental clearance, Vc and Vt the central and
peripharal volume of distribution, Vmax , the theoretical maximal
metabolic
rate and Km the MM constant.
Model 1
COMM
NPARM 5
NCON 3
nder 2
PNAMES 'CLD','VC','VMAX','KM','VT'
END
TEMP
Dose=CON(1)
TSTART = CON(2)
TSTOP = CON(3)
RATE = Dose/(TSTOP - TSTART)
CLD=P(1)
VC=P(2)
VMAX=P(3)
KM=P(4)
VT=P(5)
T=X
END
START
z(1)= 0
z(2)= 0.0
END
DIFF
If X <= TSTOP THEN
DZ(1)= RATE/VC -CLD*Z(1)/VC + CLD*Z(2)/VC - VMAX*Z(1)/(KM + Z(1))/VC
ELSE
DZ(1)= -CLD*Z(1)/VC + CLD*Z(2)/VC - VMAX*Z(1)/(KM + Z(1))/VC
ENDIF
DZ(2)= CLD*Z(1)/VT - CLD*Z(2)/VT
END
func 1
f = z(1)
end
EOM
Dr. D. Van Sassenbroeck
Heymans Institute for Pharmacology
Dept. of Pharmacology in Critical Care
De Pintelaan 185
B-9000 Gent
TEL : +32 (0)9 240 33 56
FAX : +32 (0)9 240 49 88
e-mail : diederik.vansassenbroeck.aaa.rug.ac.be
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The following message was posted to: PharmPK
Not a good day for me. I had an error pointed out in code I sent to
nmusers and now an astute PharmPk observer pointed out that I should
have written:
RateIn=ka*Z(1)
not
RateIn=ka*Z(2)
in my code for a 2 cpt mixed order first order absorption model.
Sorry for the confusion.
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
email:n.holford.at.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
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[Two responses - db]
From: "Tata, Prasad N"
Date: Tue May 13, 2003 2:07:01 PM US/Central
To: david.at.boomer.org
Subject: RE: PharmPK Re: WinNonlin User Models - three compartment model
Reply-To: "Tata, Prasad N"
The following message was posted to: PharmPK
Let me clarify what I said. I am trying to model my drug onto a
three-compartment model PK, If anyone can help me with code that I can
use
in WinNonlin I appreciate it.
Thank you very much.
Prasad Tata
Mallinckrodt, Inc.
---
From: Nick Holford
Date: Tue May 13, 2003 2:08:22 PM US/Central
To: david.at.boomer.org
Subject: Re: HELP NEEDED:user defined model in winnonlin
Reply-To: Nick Holford
The following message was posted to: PharmPK
>
> Dr Holford
> i am trying to simultaneously fit oral and IV data using user defined
> models
> in Winnonlin ver 3.1. i have used differential equations to write the
> code
> for it, however, to incorporate a Tlag (which i quess has to be in the
> form
> of INTEGRAL form) i am facing difficulties to link the intergral ORAL
> dosing
> input to the differential components.
When trying to solve differential equations you have to understand that
the initial condition is only evaluated once (at x=0). In order to made
the input rate depend on t you must put the condition on input rate not
on dose eg.
if (tDZ(1)=0
else
DZ(1)=-KA*XA
endif
PLEASE NOTE I AM NOT A WINNONLIN CONSULTANT. I RARELY USE THE PROGRAM
EXCEPT FOR
SOME SIMPLE TEACHING EXAMPLES BECAUSE I FIND NONMEM IS MUCH MORE USEFUL
FOR REAL MODELLING PROBLEMS.
> THIS IS THE CODE I TRIED WRITING AND I WOULD REALLY APPRECIATE SOME
> HELP
> FROM UR END
>
> MODEL
> remark ******************************************************
> remark Developer:
> remark Model Date: 05-11-2003
> remark Model Version: 1.0
> remark ******************************************************
> remark DOSE1 IS IV DOSE AND DOSE2 IS PO DOSE
> remark - define model-specific commands
> COMMANDS
> NFUNCTIONS 2
> NDERIVATIVES 4
> NPARAMETERS 4
> NCONSTANTS 2
> PNAMES 'KA', 'KE', 'V1', 'TL'
> PCONSTANTS 'DOSE1', 'DOSE2'
> END
> remark - define temporary variables
> TEMPORARY
> T=X
> DOSE1=CON(1)
> DOSE2=CON(2)
> IF T<=TL THEN
> DOSE2=0.0
> ELSE
> XA=DOSE2*DEXP(-KA*(T-TL))
> ENDIF
> K12=4.02
> K21=2.06
> FD=0.22
> END
> remark - define differential equations starting values
> START
> Z(1)=FD*DOSE2
> Z(2)=0
> Z(3)=0
> Z(4)=DOSE1
> END
> remark - define differential equations
> DIFFERENTIAL
> DZ(1)=-KA*XA
> DZ(2)=KA*XA+K21*Z(3)-K12*Z(2)-KE*Z(2)
> DZ(3)=K12*Z(2)-K21*Z(3)
> DZ(4)=-(KE+K12)*Z(2)+K21*Z(3)
> END
> remark - define algebraic functions
> FUNCTION 1
> F= Z(2)/V1
> END
> FUNCTION 2
> F= Z(4)/V1
> END
> remark - define any secondary parameters
> remark - end of model
> EOM
>
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
email:n.holford.at.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
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The following message was posted to: PharmPK
Hi ,
this is for trying to simultaneously fit oral and IV data using user
defined models try :
MODEL
remark DOSE1 IS IV DOSE AND DOSE2 IS PO DOSE
remark - define model-specific commands
COMMANDS
NFUN 2
NDER 5
NPARAMETERS 4
NCONSTANTS 2
PNAMES 'KA', 'KE', 'V1', 'TL'
NSEC 1
END
TEMPORARY
K12=4.02
K21=2.06
FD=0.22
DOSE1=CON(1)
DOSE2=CON(2)
END
START
Z(1)=FD*DOSE2
Z(2)=0
Z(3)=0
Z(4)=DOSE1
Z(5)=0.0
END
DIFF
t=X
if (tRATEIN=0.0
else
RATEIN=KA*Z(1)
endif
DZ(1)=-RATEIN
DZ(2)=RATEIN+K21*Z(3)-K12*Z(2)-KE*Z(2)
DZ(3)=K12*Z(2)-K21*Z(3)
DZ(4)=-(KE+K12)*Z(4)+K21*Z(5)
DZ(5)=K12*Z(4)-K21*Z(5)
END
FUNCTION 1
F= Z(2)/V1
END
FUNCTION 2
F= Z(4)/V1
END
SECO
S(1)=V1*KE
REMA
END
EOM
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