Back to the Top
The following message was posted to: PharmPK
Hi all,
We are planning to carry out oral Digoxin PK studies
in mice.
In humans,digoxin is excreted > 90% in its
unmetabolised form - mainly by renal secretion.
However, digoxin has been shown to be metabolised by
various Phase I (CYPs) and Phase II (glucoronide
formation etc) in mice. This complicates the oral
bioavailability scenario of digoxin by introducing a
metabolism component in addition to intestinal
tranport. Literature is replete with reports of use of
digoxin-ELISA kits for determination of such
metabolites.
Could anybody who is familiar with the use of such
kits share their experiences with us ? I would like to
interact further with somebody who has performed
digoxin PK in mice.
Thank You ! Will certainly appreciate any repsonse.
Regards,
Santosh Dixit
Doctoral Student
College of Pharmacy
Department of Pharmaceutical Sciences ( Biopharmaceutics)
University of Cincinnati Medical center
3223, Eden Avenue
Cincinnati , OH 45267-004
Back to the Top
[Two replies - db]
From: Roger Jelliffe
Dear Santosh:
If you are studying digoxin PK in any species, it is worth
noting that in people, the pharmacological effect does not correlate
with serum concentrations, but rather with concentrations in the
peripheral tissue compartment. Reuning et al made a very good model in
1973 showing this. We have used that model to guide clinical therapy
with our USC*PACK software for many years, and have found it most
useful. You might consider this in planning your studies. Also, in
people, about 1/3 is metabolized, 2/3 excreted, when renal function is
normal.
Some refs are:
1.Reuning R, Sams R, and Notari R: Role of Pharmacokinetics in
Drug Dosage Adjustment. Pharmacologic Effects, Kinetics, and Apparent
Volume of Distribution of Digoxin. J. Clin. Pharmacol. 13: 128-141,
1973.
2.Jelliffe R, Schumitzky A, Van Guilder M, and Jiang F: User
Manual for Version 10.7 of the USC*PACK Collection of PC Programs,
December 1, 1995. Laboratory of Applied Pharmacokinetics, USC Keck
School of Medicine, Los Angeles CA.
3.Jelliffe R, Schumitzky A, Van Guilder M, Liu M, Hu L, Maire P,
Gomis P, Barbaut X, and Tahani B: Individualizing Drug Dosage Regimens:
Roles of Population Pharmacokinetic and Dynamic Models, Bayesian
Fitting, and Adaptive Control. Ther. Drug Monit. 15: 380-393, 1993.
4.Jelliffe R: A Mathematical Analysis of Digitalis Kinetics in
Patients with Normal and Reduced Renal Function. Math. Biosci. 1:
305-320, 1967.
Very best regards,
Roger Jellliffe
Roger W. Jelliffe, M.D. Professor of Medicine,
Division of Geriatric Medicine,
Laboratory of Applied Pharmacokinetics,
USC Keck School of Medicine
2250 Alcazar St, Los Angeles CA 90033, USA
Phone (323)442-1300, fax (323)442-1302, email= jelliffe.at.usc.edu
Our web site= http://www.lapk.org
---
From: "Makram.B.R"
Hello,
CYPs seems to be a minor elimination pathway for digoxin in rodents.
It's mainly a P-gp substrate. We usually use in our lab. digoxin as a
P-gp functionality indicator in P-gp's over- and under- expression
(e.g. : Veau and al., Effect of Interleukin-2 on Intestinal
P-glycoprotein Expression and Functionality in Mice; JPET, Vol. 302,
Issue 2, 742-750, August 2002). We usually use immuno-assays to
quantify digoxin, mainly FPIA (AXSYM, Abbott) or EMIT (COBAS Mira or
others, Roche).
Hope this helps,
BEN REGUIGA Makrem
PharmD, PhDs
Pharmacokinetics and Clinical Pharmacy Lab.
Pharmacy Faculty - Paris XI - France
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)