Back to the Top
Hi everybody.
We are working with NCEs screening for its ADME. With one of the
compound, we found two peaks in plasma Conc. Vs Time profile. With the
same compound, we have done tissue distribution study also. We checked
drug concentration in liver, kidney, lungs, brain etc. In almost all the
tissue; we are getting the same profile what we have got in plasma (two
peaks).
1. I am concern with what are parameters due to which drug shows
two peak in Conc. Vs Time profile?
2. Can anyone suggest the model/method for checking the
ENTEROHEPATIC circulation of drugs (NCEs).
Regards
Mitesh Gandhi
Back to the Top
Suggest you check your assay for metabolite interference.
Michael E. Burton, Pharm.D.
Professor and Chair
Department of Pharmacy: Clinical and Administrative Sciences
College of Pharmacy
The University of Oklahoma Health Sciences Center
P. O. Box 26901, CPB211
Oklahoma City, OK 73190-5040
Back to the Top
Dear Mitesh,
You may want to look at these references:
1. J Pharm Pharmacol. 2001 Jun;53(6):901-6. Evaluation of
absorbability of centpropazine in rats: in-situ and in-vivo appraoches.
Atul BV, Paliwal JK, Gupta RC.
2. Tabata K, Yamaoka K, Fukuyama T, Nakagawa T. Evaluation of
intestinal absorption into the portal system in enterohepatic
circulation by measuring the difference in portal-venous blood
concentrations of diclofenac. Pharm Res. 1995 Jun;12(6):880-3.
4: Hoffman DJ, Seifert T, Borre A, Nellans HN. Method to estimate the
rate and extent of intestinal absorption in conscious rats using an
absorption probe and portal blood sampling.
Pharm Res. 1995 Jun;12(6):889-94.
Hope this helps in finding your answer
Manoj Khurana
Manoj Khurana, Ph. D.
Post Doctoral Fellow
Pharmacokinetics Biopharmaceutics Laboratory,
University of Maryland Baltimore
Rm 503B, HSF-II Building
20 Penn Street, Baltimore, MD 21201
Ph: 410-706-5493
Fax: 410-706-5017
Back to the Top
Mitesh,
Do you have a known or potential metabolite (such as a Phase II
conjugate) that may hydrolyze back to the original drug and possibly
undergo reabsorption in the lower GI tract? Also, are the two peaks
very close together in time, or are they many hours apart? Finally, is
this a study where the animals are fed instead of fasted?
Best Regards,
J. Christopher Spell, Ph.D.
Medical Science Liaison - Hematology/Oncology
Global Medical Communications
Wyeth Pharmaceuticals
spellj2.-a-.wyeth.com
Voicemail: 888-685-5961, Ex: 78647
Back to the Top
Tautomerization could be one of the reasons. Tautomerization is
sensitive to
pH and depending upon the pH of the mobile phase you could observe one
or
two peaks.
Thanks,
Kishore,
Kishore K. Khan, Ph. D.
Staff Scientist/Project Director
CellzDirect
8609 Cross Park Drive
Austin, TX 78754
Tel: (512) 615 2332
Fax: (512) 834 7767
Dear Mitesh,Back to the Top
You may want to use the integrated software package CTDB (Clinical
Trial DataBase) see http://www.uef.sav.sk/advanced.htm ,
to model the fate of a drug that exhibits a concentration-time profile
with two or more significant peaks. Employing this package you can
either
to determine a non-structured model (a differential equation) that
yields a phenomenological description of the drug fate (see the first
slide
at
http://www.uef.sav.sk/two_peaks.ppt ), or to build up a structured model
(a set of differential equations) that yields a physiologically
interpretable description of the drug fate (see the second slide
at http://www.uef.sav.sk/two_peaks.ppt ).
Regards,
Maria Durisova, PhD, DSc (Math/Phys)
Vice Director of Institute of Experimental Pharmacology
Slovak Academy of Sciences
and
Head of Department of Pharmacokinetics
D\0x02D9bravska cesta 9
841 04 Bratislava
Slovak Republic
Tel./Fax: +421 2 54775928
http://www.uef.sav.sk/durisova.htm
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)