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Expression of UDP-glucuronosyltransferase 1A4 in human placenta at term

Reimers, Arne LU ; Østby, Lene ; Stuen, Ina and Sundby, Eirik (2011) In European Journal of Drug Metabolism and Pharmacokinetics 35(3-4). p.79-82
Abstract

The placenta contains a large variety of metabolizing enzymes, among them UDP-glucuronosyltransferase (UGT). Several UGT2B isozymes have so far been detected in human placenta, but little is known on placental expression of UGT1A isozymes. The antiepileptic drug lamotrigine (LTG) is a UGT1A4-substrate, and its serum concentration falls by over 50% during pregnancy, leading to impaired seizure control. The placenta may be involved in this. Microsomes from term placentas of 4 LTG-users and 10 healthy control subjects were prepared. Western blot analysis detected UGT1A proteins in all placentas. The presence of UGT1A4 in placenta from LTG users was confirmed with UGT1A4 commercial standard and a specific UGT1A4 primary antibody. Since LTG... (More)

The placenta contains a large variety of metabolizing enzymes, among them UDP-glucuronosyltransferase (UGT). Several UGT2B isozymes have so far been detected in human placenta, but little is known on placental expression of UGT1A isozymes. The antiepileptic drug lamotrigine (LTG) is a UGT1A4-substrate, and its serum concentration falls by over 50% during pregnancy, leading to impaired seizure control. The placenta may be involved in this. Microsomes from term placentas of 4 LTG-users and 10 healthy control subjects were prepared. Western blot analysis detected UGT1A proteins in all placentas. The presence of UGT1A4 in placenta from LTG users was confirmed with UGT1A4 commercial standard and a specific UGT1A4 primary antibody. Since LTG is primarily metabolized by UGT1A4 and this isozyme is shown to be present in placenta at term, it may be hypothesized that the placenta is involved in the fall of LTG serum concentrations during pregnancy.

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author
; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Lamotrigine, Microsomes, Placenta, UGT
in
European Journal of Drug Metabolism and Pharmacokinetics
volume
35
issue
3-4
pages
79 - 82
publisher
Adis
external identifiers
  • pmid:21302032
  • scopus:79953773504
ISSN
0378-7966
DOI
10.1007/s13318-010-0021-x
language
English
LU publication?
no
id
8af0a405-02af-4641-bc66-b1cdfbdac3d2
date added to LUP
2024-08-31 14:52:21
date last changed
2024-09-02 13:02:08
@article{8af0a405-02af-4641-bc66-b1cdfbdac3d2,
  abstract     = {{<p>The placenta contains a large variety of metabolizing enzymes, among them UDP-glucuronosyltransferase (UGT). Several UGT2B isozymes have so far been detected in human placenta, but little is known on placental expression of UGT1A isozymes. The antiepileptic drug lamotrigine (LTG) is a UGT1A4-substrate, and its serum concentration falls by over 50% during pregnancy, leading to impaired seizure control. The placenta may be involved in this. Microsomes from term placentas of 4 LTG-users and 10 healthy control subjects were prepared. Western blot analysis detected UGT1A proteins in all placentas. The presence of UGT1A4 in placenta from LTG users was confirmed with UGT1A4 commercial standard and a specific UGT1A4 primary antibody. Since LTG is primarily metabolized by UGT1A4 and this isozyme is shown to be present in placenta at term, it may be hypothesized that the placenta is involved in the fall of LTG serum concentrations during pregnancy.</p>}},
  author       = {{Reimers, Arne and Østby, Lene and Stuen, Ina and Sundby, Eirik}},
  issn         = {{0378-7966}},
  keywords     = {{Lamotrigine; Microsomes; Placenta; UGT}},
  language     = {{eng}},
  number       = {{3-4}},
  pages        = {{79--82}},
  publisher    = {{Adis}},
  series       = {{European Journal of Drug Metabolism and Pharmacokinetics}},
  title        = {{Expression of UDP-glucuronosyltransferase 1A4 in human placenta at term}},
  url          = {{http://dx.doi.org/10.1007/s13318-010-0021-x}},
  doi          = {{10.1007/s13318-010-0021-x}},
  volume       = {{35}},
  year         = {{2011}},
}