From: "Dennis Fisher" fisher@PLessThan.com
Subject: [NMusers] Modeling of different formulations
Date: Tue, March 15, 2005 8:22 am
Colleagues,
I am dealing with the following situation:
Cohort 1: xx mg of Formulation 1
Cohort 2: xx mg of Formulation 2
Cohort 3: xx/2 mg of Formulation 1 + xx/2 mg of Formulation 2,
administered simultaneously.
Assume for the moment that the two formulations have different values
for ka and F. If I indicate in the data records which formulation is
being given (i.e., I need two separate dose records for cohort 3, one
for each formulation), F will be handled appropriately (i.e., F acts at
the time of dosing so it will apply to the dose). However, I believe
that ka will not be handled correctly for cohort 3 - whichever dose
record appears second will dictate the ka that is applied.
I could work around this by setting up two entirely separate absorption
compartments, one for each of the formulations. Does anyone have a
clever approach that solves this more simply?
Dennis
Dennis Fisher MD
P < (The "P Less Than" Company)
Phone: 1-866-PLessThan (1-866-753-7784)
Fax: 1-415-564-2220
www.PLessThan.com
Modeling of different formulations
From: "GIRARD PASCAL" PASCAL.GIRARD@adm.univ-lyon1.fr
Subject: RE : [NMusers] Modeling of different formulations
Date: Tue, March 15, 2005 8:32 am
Dear Dennis,
Why not simply treating the formulation as a covariate and having 2 separate fixed
effect parameters THETAs and random effect ETAs, one corresponding to 1st
formulation, and the 2nd one to the other formulation?
Pascal
=========================================Dr Pascal Girard
EA 3738 Ciblage Thrapeutique en Oncologie
Fac Mdecine Lyon-Sud
BP12
69921 OULLINS Cedex
France
Tel 33 4 78 86 31 53
Fax 33 4 78 86 31 49
e-mail : Pascal.Girard@adm.univ-lyon1.fr
From: "Leonid Gibiansky" leonidg@metrumrg.com
Subject: Re: [NMusers] Modeling of different formulations
Date: Tue, March 15, 2005 8:52 am
Dennis,
Each dose can have its own F, so you are able to control F for those two
formulations. However, KA is the characteristic of the system. As soon as drug is placed into the depot
compartment, you cannot distinguish which formulation it came from. Therefore, the only way to have
two KAs for cohort 3 is to have two compartments, one for each formulation.
Leonid
From: "Nick Holford" n.holford@auckland.ac.nz
Subject: Re: [NMusers] Modeling of different formulations
Date: Tue, March 15, 2005 9:35 am
Denis,
If this is a single dose or regular multiple dosing then you easily write an
explicit solution for each type of formulation in $PRED i.e. forget about using
PREDPP.
Nick
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
From: "Bachman, William (MYD)" bachmanw@iconus.com
Subject: RE: [NMusers] Modeling of different formulations
Date: Tue, March 15, 2005 10:00 am
Writing your own $PRED is more (user-induced) error prone and you lose
dosing flexibility compared to PREDPP. I would suggest differential
equation model unless you already have a canned PRED model.
From: "Masaki Hiraoka" masaki.hiraoka@bms.com
Subject: Re: [NMusers] Modeling of different formulations
Date: Fri, March 18, 2005 12:32 am
Dear nmusers,
I'm trying to use subroutines such like INFN with $PRED.
Does anyone know how to implement a user supplied subroutine after
estimation step?
Could anyone provide me with an example?
Thanks in advance.
Masaki Hiraoka
From: "Bachman, William (MYD)" bachmanw@iconus.com
Subject: RE: [NMusers] Modeling of different formulations
Date: Fri, March 18, 2005 7:57 am
Try searching at http://www.cognigencorp.com/nonmem/sitesearch/index.html
The NONMEM UsersNet Archive
nmconsult@globomaxnm.com
GloboMax
The Strategic Pharmaceutical Development Division of ICON plc
7250 Parkway Drive, Suite 430
Hanover, MD 21076
Voice: (410) 782-2205
FAX: (410) 712-0737
_______________________________________________________
From: "GIRARD PASCAL" PASCAL.GIRARD@adm.univ-lyon1.fr
Subject: RE : [NMusers] Modeling of different formulations
Date:
Oups! Leonid gives the correct answer to my question: since as he states when a drug
is placed into the depot compartment,NONMEM cannot distinguish which formulation it
came from, use of formulation as a covariate will be useless for Ka, and so 2
separate depot compartments will be needed.
Pascal
=========================================Dr Pascal Girard
EA 3738 Ciblage Thrapeutique en Oncologie
Fac Mdecine Lyon-Sud
BP12
69921 OULLINS Cedex
France
Tel 33 4 78 86 31 53
Fax 33 4 78 86 31 49
e-mail : Pascal.Girard@adm.univ-lyon1.fr