From: Johan.Rosenborg@astrazeneca.com
Subject: [NMusers] PD interaction between two substances
Date: Mon, April 5, 2004 8:01 am
All,
I would like to model a pharmacodynamic interaction between two substance -
denoted "1" and "2" below - assumingly with a common Emax-value but with
different EC50-values - EC50(1) and EC50(2) - using the equation below
(adapted from a text book on receptor theory by T P Kenakin):
Effect = Emax X {1/(1 + EC50(1)/[C(1)] X (1 + [C(2)]/EC50(2)) + 1/(1 +
EC50(2)/[C(2)] X (1 + [C(1)]/EC50(1))}, where
Effect =Total effect of substance 1 and substance 2
Emax =Common maximum effect of substance 1 and substance 2
EC50(1)=Concentration of substance 1 giving half maximum effect
EC50(2)=Concentration of substance 2 giving half maximum effect
C(1) = concentration of substance 1
C(2) = concentration of substance 2
My question: There are several examples in the NONMEM help guide on how to
transform PK- to PD-data under $ERROR in the model file using one
PK-variable (PK_PD_simultaneous_1-4), but how can I do my case with two
PK-variables?
Johan
Johan Rosenborg
AstraZeneca R&D Lund
Experimental Medicine, S-221 87 Lund, Sweden
Tel: +46 46 33 65 99 Fax: +46 46 33 71 91
E-mail: johan.rosenborg@astrazeneca.com
PD interaction between two substances
From: Bachman, William (MYD) bachmanw@iconus.com
Subject: RE: [NMusers] PD interaction between two substances
Date: Mon, April 5, 2004 9:15 am
Johan,
Do I understand your question correctly: "how do I fit simultaneously PK and
PD data simultaneously if I have two different PK observations and one PD
observation?".
If so, you have to structure your model so that each observation is modeled
in a different compartment. Then instead of a binary switching mechanism
based on the CMT data, you have to construct a switch based on three
compartments. There may be some nuances I have not considered, but,
basically:
$ERROR
;IF CMT=1 for C(1), CMT=2 for C(2), CMT=3 for Effect
C1=A(1)/V1
C2=A(2)/V2
IF (CT.EQ.3) THEN
Y=Emax *(1/(1 + EC51/C1)* (1 + C2/EC52) + 1/(1 + EC52)/(C2) * (1 + C1/EC51))
+ ERR(3)
ELSEIF (CMT.EQ.1) THEN
Y =F*EXP(ERR(1)) ;F is pred in CMT 1 here
ELSE
Y =F*EXP(ERR(2)) ;F is pred in CMT 2 here
ENDIF
;check for typos in above
Bill
William J. Bachman, Ph.D.
Manager, Pharmacometrics Research and Development
GloboMax
The Strategic Pharmaceutical Development Division of ICON plc
7250 Parkway Drive, Suite 430
Hanover, MD 21076
410-782-2212
bachmanw@iconus.com
From: drfreedman@drfreedmaninc.com
Subject: RE: :[NMusers] PD interaction between two substances
Date: Mon, April 5, 2004 10:57 am
Johan
Why not consider 2 sets of PK compartments and 1 set of PD
compartments with explicit equations under ADVAN6?
Immanuel Freedman, PhD, MIEEE
Dr. Immanuel Freedman, Inc.
(619) 884-1347
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