Strong Inhibition of UDP-Glucuronosyltransferase (UGT) 1A1 by Levothyroxine Indicates the Potential UGT-Inhibition Based Adverse Effect of Levothyroxine

UDP-glucuronosyltransferase (UGT) 1A1, one of the most important UGT isoforms, can metabolize a variety of endogenous substances and xenobiotics. UGT1A1-catalyzed glucuronidation reaction plays a key role in many clinical events, including Gilbert syndrome and irrinotecan-induced diarrhea toxicity....

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Autores principales: Zhao, Hua-Dong, Bao, Guo-Qiang, He, Xian-Li, Wu, Tao, Wang, Cheng-Guo, Wang, Sheng-Zhi, Zang, Li, Lu, Jian-Guo, Du, Xi-Lin
Formato: Articulo Comunicacion
Lenguaje:Inglés
Publicado: 2012
Materias:
Farmacia
Glucuronosiltransferasa
Levothyroxine
UDP-glucuronosyltransferase (UGT) 1A1
Drug-drug interaction
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/20236
http://www.latamjpharm.org/resumenes/31/5/LAJOP_31_5_2_5.pdf
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-20236
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
Levothyroxine
UDP-glucuronosyltransferase (UGT) 1A1
Drug-drug interaction
spellingShingle Farmacia
Glucuronosiltransferasa
Levothyroxine
UDP-glucuronosyltransferase (UGT) 1A1
Drug-drug interaction
Zhao, Hua-Dong
Bao, Guo-Qiang
He, Xian-Li
Wu, Tao
Wang, Cheng-Guo
Wang, Sheng-Zhi
Zang, Li
Lu, Jian-Guo
Du, Xi-Lin
Strong Inhibition of UDP-Glucuronosyltransferase (UGT) 1A1 by Levothyroxine Indicates the Potential UGT-Inhibition Based Adverse Effect of Levothyroxine
topic_facet Farmacia
Glucuronosiltransferasa
Levothyroxine
UDP-glucuronosyltransferase (UGT) 1A1
Drug-drug interaction
description UDP-glucuronosyltransferase (UGT) 1A1, one of the most important UGT isoforms, can metabolize a variety of endogenous substances and xenobiotics. UGT1A1-catalyzed glucuronidation reaction plays a key role in many clinical events, including Gilbert syndrome and irrinotecan-induced diarrhea toxicity. The present study aims to investigate the inhibition of UGT1A1 by levothyroxine which is clinically used to treat thyroid hormone deficiency, and occasionally to prevent the recurrence of thyroid cancer. The recombinant UGT1A1was used as enzyme source, and 4-methylumbelliferone (4-MU) was utilized as a non-specific probe substrate. The results showed that levothyroxine inhibited the UGT1A1-catalyzed 4- MU glucuronidation in a dose-dependent manner. Furthermore, Lineweaver-Burk and Dixon plots showed that the inhibition of UGT1A1 by levothyroxine was best fit to the competitive inhibition type, and the inhibition kinetic parameter (Ki ) was calculated to be 1 μM. Taken together, the competitive of levothyroxine towards UGT1A1 was demonstrated in the present study, which might induce severe clinical results, including potential drug-drug interaction and metabolic disorders of endogenous substances.
format Articulo
Comunicacion
author Zhao, Hua-Dong
Bao, Guo-Qiang
He, Xian-Li
Wu, Tao
Wang, Cheng-Guo
Wang, Sheng-Zhi
Zang, Li
Lu, Jian-Guo
Du, Xi-Lin
author_facet Zhao, Hua-Dong
Bao, Guo-Qiang
He, Xian-Li
Wu, Tao
Wang, Cheng-Guo
Wang, Sheng-Zhi
Zang, Li
Lu, Jian-Guo
Du, Xi-Lin
author_sort Zhao, Hua-Dong
title Strong Inhibition of UDP-Glucuronosyltransferase (UGT) 1A1 by Levothyroxine Indicates the Potential UGT-Inhibition Based Adverse Effect of Levothyroxine
title_short Strong Inhibition of UDP-Glucuronosyltransferase (UGT) 1A1 by Levothyroxine Indicates the Potential UGT-Inhibition Based Adverse Effect of Levothyroxine
title_full Strong Inhibition of UDP-Glucuronosyltransferase (UGT) 1A1 by Levothyroxine Indicates the Potential UGT-Inhibition Based Adverse Effect of Levothyroxine
title_fullStr Strong Inhibition of UDP-Glucuronosyltransferase (UGT) 1A1 by Levothyroxine Indicates the Potential UGT-Inhibition Based Adverse Effect of Levothyroxine
title_full_unstemmed Strong Inhibition of UDP-Glucuronosyltransferase (UGT) 1A1 by Levothyroxine Indicates the Potential UGT-Inhibition Based Adverse Effect of Levothyroxine
title_sort strong inhibition of udp-glucuronosyltransferase (ugt) 1a1 by levothyroxine indicates the potential ugt-inhibition based adverse effect of levothyroxine
publishDate 2012
url http://sedici.unlp.edu.ar/handle/10915/20236
http://www.latamjpharm.org/resumenes/31/5/LAJOP_31_5_2_5.pdf
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