From: bvatul [mailto:bvatul@ufl.edu]
Subject: Conversion of micro constants to macro constants
Date: Tue, 14 Aug 2001
Hello All
Could somebody share their views on this?
I am analysing a data set (iv infusion) in NONMEM using a three compartment
model for the drug and two compartment model for the metabolite using
ADVAN6. How can I calculate the macro constants (alpha, beta, gamma) from
the calculated microconstants (k10, k12, k21, k13, k31, k30)? I wish to
estimate the half-life etc. Are there any reported papers on these type of
results?
Thanks in advance
Atul
Conversion of micro constants to macro constants
From: "Bachman, William" <bachmanw@globomax.com>
Subject: RE: Conversion of micro constants to macro constants
Date: Tue, 14 Aug 2001 13:58:03 -0400
The conversion formulas can be found in the help guide, NONMEM Users Guide
VIII, under TRANS4 entry, page 293. (rearrange first)
William J. Bachman, Ph.D.
GloboMax LLC
7250 Parkway Dr., Suite 430
Hanover, MD 21076
Voice (410) 782-2212
FAX (410) 712-0737
bachmanw@globomax.com
From: "Bachman, William" <bachmanw@globomax.com>
Subject: RE: Conversion of micro constants to macro constants
Date: Tue, 14 Aug 2001 14:00:56 -0400
oops!! you wanted alpha, beta, gamma - TRANS6, p.296
also probably in Wagner's book.
From: "Bachman, William" <bachmanw@globomax.com>
Subject: RE: Conversion of micro constants to macro constants
Date: Tue, 14 Aug 2001 14:46:20 -0400
Atul,
The explicit solutions to the cubic equations are given in JPB 2(4),
299-312, 1974. But beware, I believe there are typos in the equations:
1. the "+" sign in eqn(10) should be a multiplication
2. eqns(11) and (12) appear to have been switched (10 is -beta, 11 is
-alpha)
Bill
From: "Joern Loetsch" <j.loetsch@em.uni-frankfurt.de>
Subject: Re: Conversion of micro constants to macro constants
Date: Tue, 14 Aug 2001 21:18:46 +0200
There is an Excel spread sheet doing this, developed by Dr. Steven =
Shafer, Stanford. It can be downloaded from
http://pkpd.icon.palo-alto.med.va.gov/
However, the link was down right now.
Jorn Lotsch
_______________________________________________________
Jorn Lotsch, MD
pharmazentrum frankfurt, Department of Clinical Pharmacology
Johann Wolfgang Geothe-University Hospital
Theodor-Stern-Kai 7
D-60590 Frankfurt
Germany
Phone: +49-69-6301-4589
Fax: +49-69-6301-7636
From: "Bachman, William" <bachmanw@globomax.com>
Subject: RE: Conversion of micro constants to macro constants - YAC (yet a nother correction)
Date: Tue, 14 Aug 2001 15:51:10 -0400
1. the "+" sign in eqn(10) should be a DIVISION.
One should not shoot from the hip, unless brain is connected to hip!
From: Janet Wade <jwade@pharsight.com>
Subject: RE: Conversion of micro constants to macro constants
Date: Tue, 14 Aug 2001 13:08:03 -0700
This link has been down for ages, is this site still available to us?
Janet
From: "Whitfield, Lloyd" <Lloyd.Whitfield@pfizer.com>
Subject: RE: Conversion of micro constants to macro constants
Date: Tue, 14 Aug 2001 16:34:13 -0400
Atul,
You can solve the cubic equation for the 3-compartment model to get the
macroconstants using verbatim code. NONMEM does not have all of the trig
functions necessary to solve the equations but you can gain access to the
trig function in the fortran compiler using verbatim code. The verbatim code
is denoted by the lines with " in the left most column. I did in within the
control stream but it could also be done an INFN subroutine. I include a
copy of my control stream for your reference.
Regards,
Lloyd
Lloyd Whitfield
Clinical Sciences
Email: lloyd.whitfield@pfizer.com
Phone: 734-622-7023
Bldg. 50/100
From: Lutz.Harnisch@aventis.com
Subject: AW: Conversion of micro constants to macro constants
Date: Wed, 15 Aug 2001 10:23:52 +0200
The lambdas (alpha, beta, gamma) can numerically be calculated by evaluating
the Eigenvalues from the Eigenmatrix. The Eigenmatrix is constructed from
the linear DES. See Splus guide on eigen() for references.
The special case for an example of a mammilary model is given below as Splus
code, but any other linear DES could be handled in equivalently.
____________________________________
k10 <- 1.486
k12 <- 0.351
k21 <- 0.080
k13 <- 1.703
k31 <- 0.633
print(c(k10, k12, k21, k13, k31))
dg <- matrix(NA,3,3)
dg[1, ] <- c( - k10 - k12 - k13, k21, k31)
dg[2, ] <- c( k12 , - k21, 0)
dg[3, ] <- c( k13, 0, - k31)
print(dg)
print(-eigen(dg)$values)
_____________________________________
Lutz Harnisch
DMPK PopKin
Aventis Pharma
Frankfurt
Germany