In vitro metabolism and in vivo pharmacokinetics of quinoline 3-carboxamide derivatives in various species
(2005) In Xenobiotica 35(3). p.293-304- Abstract
- The metabolism of a group of quinoline 3-carboxamide derivatives was evaluated in liver microsomes from various species. In addition, metabolism data were compared with in vivo pharmacokinetics in the mouse. The studied compounds were metabolized by cytochrome P450 enzymes. Microsomal clearance was low and seemed independent of a substituent in the quinoline moiety, whereas clearance was enhanced when an ethyl group replaced the methyl group at the carboxamide position. A similar metabolism with hydroxylated and dealkylated metabolites was found in the various species, with quantitative differences due to substituent. As predicted from the in vitro studies, in vivo pharmacokinetics showed low clearance and thus high exposure of the parent... (More)
- The metabolism of a group of quinoline 3-carboxamide derivatives was evaluated in liver microsomes from various species. In addition, metabolism data were compared with in vivo pharmacokinetics in the mouse. The studied compounds were metabolized by cytochrome P450 enzymes. Microsomal clearance was low and seemed independent of a substituent in the quinoline moiety, whereas clearance was enhanced when an ethyl group replaced the methyl group at the carboxamide position. A similar metabolism with hydroxylated and dealkylated metabolites was found in the various species, with quantitative differences due to substituent. As predicted from the in vitro studies, in vivo pharmacokinetics showed low clearance and thus high exposure of the parent compounds in the mouse. The therapeutic effect seen in the acute EAE mouse model for these related compounds seems dependent on the high exposure of parent compound rather than formation of any potentially active metabolites. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/236372
- author
- Tuvesson, Helen LU ; Hallin, I ; Ellman, M ; Sparre, B ; Gunnarsson, PO and Seidegard, J
- organization
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- quinoline 3-carboxamides, metabolism, pharmacokinetics
- in
- Xenobiotica
- volume
- 35
- issue
- 3
- pages
- 293 - 304
- publisher
- Taylor & Francis
- external identifiers
-
- pmid:16019952
- wos:000229621800006
- scopus:20144376334
- ISSN
- 0049-8254
- DOI
- 10.1080/00498250500066329
- language
- English
- LU publication?
- yes
- id
- 0398abcc-766c-4d04-b108-8b8fc435a858 (old id 236372)
- date added to LUP
- 2016-04-01 16:14:39
- date last changed
- 2022-01-28 18:17:44
@article{0398abcc-766c-4d04-b108-8b8fc435a858,
abstract = {{The metabolism of a group of quinoline 3-carboxamide derivatives was evaluated in liver microsomes from various species. In addition, metabolism data were compared with in vivo pharmacokinetics in the mouse. The studied compounds were metabolized by cytochrome P450 enzymes. Microsomal clearance was low and seemed independent of a substituent in the quinoline moiety, whereas clearance was enhanced when an ethyl group replaced the methyl group at the carboxamide position. A similar metabolism with hydroxylated and dealkylated metabolites was found in the various species, with quantitative differences due to substituent. As predicted from the in vitro studies, in vivo pharmacokinetics showed low clearance and thus high exposure of the parent compounds in the mouse. The therapeutic effect seen in the acute EAE mouse model for these related compounds seems dependent on the high exposure of parent compound rather than formation of any potentially active metabolites.}},
author = {{Tuvesson, Helen and Hallin, I and Ellman, M and Sparre, B and Gunnarsson, PO and Seidegard, J}},
issn = {{0049-8254}},
keywords = {{quinoline 3-carboxamides; metabolism; pharmacokinetics}},
language = {{eng}},
number = {{3}},
pages = {{293--304}},
publisher = {{Taylor & Francis}},
series = {{Xenobiotica}},
title = {{In vitro metabolism and in vivo pharmacokinetics of quinoline 3-carboxamide derivatives in various species}},
url = {{http://dx.doi.org/10.1080/00498250500066329}},
doi = {{10.1080/00498250500066329}},
volume = {{35}},
year = {{2005}},
}