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Regional transport and metabolism of roivacaine and its CYP3A4 metabolite PPX in human intestine

Berggren, S; Lennernas, P; Ekelund, Mats LU ; Weström, Björn LU ; Hoogstraate, J and Lennernas, H (2003) In Journal of Pharmacy and Pharmacology 55(7). p.963-972
Abstract
The major aim of this study was to investigate the CYP3A4 metabolism and polarized transport of ropivacaine and its metabolite 2',6'-pipecoloxylidide (PPX) in tissue specimens from the human small and large intestine. Ropivacaine has been shown to be effective in the treatment of ulcerative colitis in human colon. This study was conducted using a modified Ussing-chamber technique with specimens from jejunum, ileum and colon collected from 11 patients. The local kinetics of ropivacaine and PPX were assessed from their concentration-time profiles in mucosal and serosal compartments. The permeability (P-app) in the absorptive direction for both ropivacaine and PPX increased regionally in the order jejunum <ileum<colon. Ropivacaine was... (More)
The major aim of this study was to investigate the CYP3A4 metabolism and polarized transport of ropivacaine and its metabolite 2',6'-pipecoloxylidide (PPX) in tissue specimens from the human small and large intestine. Ropivacaine has been shown to be effective in the treatment of ulcerative colitis in human colon. This study was conducted using a modified Ussing-chamber technique with specimens from jejunum, ileum and colon collected from 11 patients. The local kinetics of ropivacaine and PPX were assessed from their concentration-time profiles in mucosal and serosal compartments. The permeability (P-app) in the absorptive direction for both ropivacaine and PPX increased regionally in the order jejunum <ileum<colon. Ropivacaine was not found to be subjected to any carrier-mediated intestinal efflux. However, the CYP3A4 metabolite left the human enterocyte in a polarized manner and both the extent of CYP3A4 metabolism of ropivacaine and the extrusion of its metabolite to the mucosal chamber were more efficient in jejunum than in ileum. P-glycoprotein was probably not involved in the metabolite extrusion. No other metabolite than PPX was found. This in-vitro study with human intestinal tissues provides new mechanistic insights into regional transport and metabolism of drugs. (Less)
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organization
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Contribution to journal
publication status
published
subject
in
Journal of Pharmacy and Pharmacology
volume
55
issue
7
pages
963 - 972
publisher
Pharmaceutical Press
external identifiers
  • wos:000184918000009
  • pmid:12906753
  • scopus:0041664961
ISSN
0022-3573
DOI
language
English
LU publication?
yes
id
657577e1-2b6c-4df4-90bd-c67281a8ac9f (old id 303417)
date added to LUP
2007-08-23 08:26:06
date last changed
2018-06-10 04:34:14
@article{657577e1-2b6c-4df4-90bd-c67281a8ac9f,
  abstract     = {The major aim of this study was to investigate the CYP3A4 metabolism and polarized transport of ropivacaine and its metabolite 2',6'-pipecoloxylidide (PPX) in tissue specimens from the human small and large intestine. Ropivacaine has been shown to be effective in the treatment of ulcerative colitis in human colon. This study was conducted using a modified Ussing-chamber technique with specimens from jejunum, ileum and colon collected from 11 patients. The local kinetics of ropivacaine and PPX were assessed from their concentration-time profiles in mucosal and serosal compartments. The permeability (P-app) in the absorptive direction for both ropivacaine and PPX increased regionally in the order jejunum &lt;ileum&lt;colon. Ropivacaine was not found to be subjected to any carrier-mediated intestinal efflux. However, the CYP3A4 metabolite left the human enterocyte in a polarized manner and both the extent of CYP3A4 metabolism of ropivacaine and the extrusion of its metabolite to the mucosal chamber were more efficient in jejunum than in ileum. P-glycoprotein was probably not involved in the metabolite extrusion. No other metabolite than PPX was found. This in-vitro study with human intestinal tissues provides new mechanistic insights into regional transport and metabolism of drugs.},
  author       = {Berggren, S and Lennernas, P and Ekelund, Mats and Weström, Björn and Hoogstraate, J and Lennernas, H},
  issn         = {0022-3573},
  language     = {eng},
  number       = {7},
  pages        = {963--972},
  publisher    = {Pharmaceutical Press},
  series       = {Journal of Pharmacy and Pharmacology},
  title        = {Regional transport and metabolism of roivacaine and its CYP3A4 metabolite PPX in human intestine},
  url          = {http://dx.doi.org/},
  volume       = {55},
  year         = {2003},
}