> Dear NMusers,
I am using a dual absorption model as follows (The dose is split into 2
fractions and the splitting fraction, THETA(.), is an estimated parameter in
the model):
TPH = LOG(THETA(.)/(1-THETA(.)))
TH = EXP(TPH+ETA(.))/(1+EXP(TPH+ETA(.)))
F2 = TH
F1 = 1-TH
However, upon prolonged sampling we can observe a 3rd shallow phase. I would
like to use a 3-depot absorption process with F1, F2 and F3=1-F1-F2. Both F1
and F2 need etas using some type of transformation such that neither one of
them exceed 1 nor does their sum exceed 1. Can some one kindly provide the
NONMEM code.
Thanking you in advance,
Mahesh
Coding a triple absorption model
Title: Coding a triple absorption model
Mahesh, Consider modeling F2 as a fraction of the part of bioavailablilty left over after F1: LF1 = THETA(1)*EXP(ETA(1)) F1= LF1/(1+LF1) LF2 = THETA(2)*EXP(ETA(2)) F2 = (1-F1)*(LF2/(1+LF2)) ;LF2 DESCRIBES FRACTION OF THE STILL AVAILABLE DOSE (1-F1) F3 = 1-F1-F2 Mark Sale MD
Next Level Solutions, LLC
www.NextLevelSolns.com
919-846-9185
Quoted reply history
-------- Original Message --------
Subject: [NMusers] Coding a triple absorption model
From: "Samtani, Mahesh [PRDUS]" < [email protected] >
Date: Thu, June 04, 2009 4:34 pm
To: < [email protected] >
Dear NMusers, I am using a dual absorption model as follows (The dose is split into 2 fractions and the splitting fraction, THETA(.), is an estimated parameter in the model): TPH = LOG(THETA(.)/(1-THETA(.))) TH = EXP(TPH+ETA(.))/(1+EXP(TPH+ETA(.))) F2 = TH F1 = 1-TH However, upon prolonged sampling we can observe a 3rd shallow phase. I would like to use a 3-depot absorption process with F1, F2 and F3=1-F1-F2. Both F1 and F2 need etas using some type of transformation such that neither one of them exceed 1 nor does their sum exceed 1. Can some one kindly provide the NONMEM code. Thanking you in advance, Mahesh
Hello Mahesh,
I recommend that your read the following paper:
The use of a sum of inverse Gaussian functions to describe the absorption
profile of drugs exhibiting complex absorption.Csajka C, Drover D, Verotta D.
Pharm Res. 2005 Aug;22(8):1227-35. Epub 2005 Aug 3.
It details how to constraint F's when you have multiple absorption components
as in your case. It includes two different methods for parametrization(P1) and
(P2) as well as useful equations that can be coded into nonmem easily.
Hope this helps,
Samer
Quoted reply history
-----Original Message-----
From: [email protected] on behalf of Samtani, Mahesh [PRDUS]
Sent: Thu 6/4/2009 16:34
To: [email protected]
Subject: [NMusers] Coding a triple absorption model
> Dear NMusers,
I am using a dual absorption model as follows (The dose is split into 2
fractions and the splitting fraction, THETA(.), is an estimated parameter in
the model):
TPH = LOG(THETA(.)/(1-THETA(.)))
TH = EXP(TPH+ETA(.))/(1+EXP(TPH+ETA(.)))
F2 = TH
F1 = 1-TH
However, upon prolonged sampling we can observe a 3rd shallow phase. I would
like to use a 3-depot absorption process with F1, F2 and F3=1-F1-F2. Both F1
and F2 need etas using some type of transformation such that neither one of
them exceed 1 nor does their sum exceed 1. Can some one kindly provide the
NONMEM code.
Thanking you in advance,
Mahesh
SUM=1+ EXP(THETA(1)+ETA(1)) + EXP(THETA(2)+ETA(2))
F1=EXP(THETA(1)+ETA(1))/SUM
F2=EXP(THETA(2)+ETA(2))/SUM
F3=1/SUM
--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566
Samtani, Mahesh [PRDUS] wrote:
> Dear NMusers,
>
> I am using a dual absorption model as follows (The dose is split into 2 fractions and the splitting fraction, THETA(.), is an estimated parameter in the model):
>
> TPH = LOG(THETA(.)/(1-THETA(.)))
> TH = EXP(TPH+ETA(.))/(1+EXP(TPH+ETA(.)))
> F2 = TH
> F1 = 1-TH
>
> However, upon prolonged sampling we can observe a 3rd shallow phase. I would like to use a 3-depot absorption process with F1, F2 and F3=1-F1-F2. Both F1 and F2 need etas using some type of transformation such that neither one of them exceed 1 nor does their sum exceed 1. Can some one kindly provide the NONMEM code.
>
> Thanking you in advance,
> Mahesh