Levothyroxine Exhibits Inhibitory Effect towards UDP-Glucuronosyltransferase (UGT) 1A6-Mediated 4-Methylumbelliferone (4-MU) Glucuronidation

Levothyroxine, a synthetic form of thyroid hormone, has been clinically used to treat thyroid hormone deficiency. UDP-glucuronosyltransferases (UGTs) are important phase II drug-metabolizing enzymes, and UGTs-inhibition based drug-drug interaction has been widely reported. The aim of the present stu...

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Autores principales: Wang, Chuan-Qiang, Song, Ming-Zhu, Zhu, Hou-Wei, Yi, Jia-Jun, Luan, Ming-Chun, Shi, Ai-Yuan, Qu, Yan-Qing
Formato: Articulo Comunicacion
Lenguaje:Inglés
Publicado: 2012
Materias:
Farmacia
Glucuronosiltransferasa
Drug-drug interaction
Levothyroxine
UDP-glucuronosyltransferases (UGTs)
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/20228
http://www.latamjpharm.org/resumenes/31/5/LAJOP_31_5_2_1.pdf
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-20228
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Farmacia
Glucuronosiltransferasa
Drug-drug interaction
Levothyroxine
UDP-glucuronosyltransferases (UGTs)
spellingShingle Farmacia
Glucuronosiltransferasa
Drug-drug interaction
Levothyroxine
UDP-glucuronosyltransferases (UGTs)
Wang, Chuan-Qiang
Song, Ming-Zhu
Zhu, Hou-Wei
Yi, Jia-Jun
Luan, Ming-Chun
Shi, Ai-Yuan
Qu, Yan-Qing
Levothyroxine Exhibits Inhibitory Effect towards UDP-Glucuronosyltransferase (UGT) 1A6-Mediated 4-Methylumbelliferone (4-MU) Glucuronidation
topic_facet Farmacia
Glucuronosiltransferasa
Drug-drug interaction
Levothyroxine
UDP-glucuronosyltransferases (UGTs)
description Levothyroxine, a synthetic form of thyroid hormone, has been clinically used to treat thyroid hormone deficiency. UDP-glucuronosyltransferases (UGTs) are important phase II drug-metabolizing enzymes, and UGTs-inhibition based drug-drug interaction has been widely reported. The aim of the present study is to investigate the inhibitory effect of levothyroxine towards UGT1A6-catalyzed 4-methylumbelliferone (4-MU) glucuronidation. The results showed that levothyroxine inhibited UGT1A6-catalyzed 4-MU glucuronidation reaction in a dose-dependent manner. Furthermore, Lineweaver-Burk and Dixon plots showed the inhibition of UGT1A6 by levothyroxine was best fit to competitive inhibition, and the inhibition kinetic parameter (Ki ) was determined to be 15.3 μM. Given that UGT1A6 is one of the most important UGT isoforms catalyzing the glucuronidation reaction of many important clinical drugs, including aspirin and serotonin, inhibition of UGT1A6 activity by levothyroxine will significantly influence the pharmacokinetic behaviour of these drugs. Therefore, clinical drug-drug interaction due to the inhibition of UGT1A6 by levothyroxine should paid much attention.
format Articulo
Comunicacion
author Wang, Chuan-Qiang
Song, Ming-Zhu
Zhu, Hou-Wei
Yi, Jia-Jun
Luan, Ming-Chun
Shi, Ai-Yuan
Qu, Yan-Qing
author_facet Wang, Chuan-Qiang
Song, Ming-Zhu
Zhu, Hou-Wei
Yi, Jia-Jun
Luan, Ming-Chun
Shi, Ai-Yuan
Qu, Yan-Qing
author_sort Wang, Chuan-Qiang
title Levothyroxine Exhibits Inhibitory Effect towards UDP-Glucuronosyltransferase (UGT) 1A6-Mediated 4-Methylumbelliferone (4-MU) Glucuronidation
title_short Levothyroxine Exhibits Inhibitory Effect towards UDP-Glucuronosyltransferase (UGT) 1A6-Mediated 4-Methylumbelliferone (4-MU) Glucuronidation
title_full Levothyroxine Exhibits Inhibitory Effect towards UDP-Glucuronosyltransferase (UGT) 1A6-Mediated 4-Methylumbelliferone (4-MU) Glucuronidation
title_fullStr Levothyroxine Exhibits Inhibitory Effect towards UDP-Glucuronosyltransferase (UGT) 1A6-Mediated 4-Methylumbelliferone (4-MU) Glucuronidation
title_full_unstemmed Levothyroxine Exhibits Inhibitory Effect towards UDP-Glucuronosyltransferase (UGT) 1A6-Mediated 4-Methylumbelliferone (4-MU) Glucuronidation
title_sort levothyroxine exhibits inhibitory effect towards udp-glucuronosyltransferase (ugt) 1a6-mediated 4-methylumbelliferone (4-mu) glucuronidation
publishDate 2012
url http://sedici.unlp.edu.ar/handle/10915/20228
http://www.latamjpharm.org/resumenes/31/5/LAJOP_31_5_2_1.pdf
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