Tacrolimus (Tacro) strongly inhibits intestinal UDP-glucuronosyltransferase (UGT) 1A8

Tacrolimus (Brand name: Prograf), a kind of immunosuppressants, has been reported to induce drug-drug interaction with many clinical drugs. Tacrolimus-mycophenolic acid (MPA) interaction has been widely and frequently reported. Intestinal UDP-glucuronosyltransferase (UGT) 1A8-mediated metabolism pla...

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Detalles Bibliográficos
Autores principales:	Yu, Jian, Wang, Chuan-Qiang, Fang, Long-Hao, Li, Meng, Wang, Xiangyang, Dai, Lu-Lu, Gao, Ya-Jie
Formato:	Articulo Comunicacion
Lenguaje:	Inglés
Publicado:	2012
Materias:	Farmacia Drug-Drug Interaction (DDI) Mycophenolic Acid (MPA) Tacrolimus UDP-Glucuronosyltransferase (UGT) 1A8 Glucuronosiltransferasa Ácido Micofenólico
Acceso en línea:	http://sedici.unlp.edu.ar/handle/10915/20208 http://www.latamjpharm.org/resumenes/31/4/LAJOP_31_4_2_3.pdf
Aporte de:	SEDICI (UNLP) de Universidad Nacional de La Plata

id	I19-R120-10915-20208
record_format	dspace
institution	Universidad Nacional de La Plata
institution_str	I-19
repository_str	R-120
collection	SEDICI (UNLP)
language	Inglés
topic	Farmacia Drug-Drug Interaction (DDI) Mycophenolic Acid (MPA) Tacrolimus UDP-Glucuronosyltransferase (UGT) 1A8 Glucuronosiltransferasa Ácido Micofenólico
spellingShingle	Farmacia Drug-Drug Interaction (DDI) Mycophenolic Acid (MPA) Tacrolimus UDP-Glucuronosyltransferase (UGT) 1A8 Glucuronosiltransferasa Ácido Micofenólico Yu, Jian Wang, Chuan-Qiang Fang, Long-Hao Li, Meng Wang, Xiangyang Dai, Lu-Lu Gao, Ya-Jie Tacrolimus (Tacro) strongly inhibits intestinal UDP-glucuronosyltransferase (UGT) 1A8
topic_facet	Farmacia Drug-Drug Interaction (DDI) Mycophenolic Acid (MPA) Tacrolimus UDP-Glucuronosyltransferase (UGT) 1A8 Glucuronosiltransferasa Ácido Micofenólico
description	Tacrolimus (Brand name: Prograf), a kind of immunosuppressants, has been reported to induce drug-drug interaction with many clinical drugs. Tacrolimus-mycophenolic acid (MPA) interaction has been widely and frequently reported. Intestinal UDP-glucuronosyltransferase (UGT) 1A8-mediated metabolism plays a key role in the elimination of MPA, and alteration of the activity of UGT1A8 resulting from gene polymorphisms could significantly influence the catalyzing activity of MPA glucuronidation. The aim of the present study is to investigate the inhibitory potential of tacrolimus towards UGT1A8, which was speculated to be a potential cause for tacrolimus-MPA interaction. The recombinant UGT1A8 was used as enzyme source, and a nonspecific substrate 4-methylumbelliferone (4-MU) was utilized as substrate. The results showed that 100 μM of tacrolimus inhibited UGT1A8-mediated 4-MU glucuronidation activity by 82.3%. Further inhibition kinetic investigation showed that the inhibition of UGT1A8 by tacrolimus was best fit to competitive inhibition type, and the inhibition kinetic parameter (Ki) was determined to be 6.1 μM. All these results indicated that tacrolimus could exhibit strong inhibition towards UGT1A8, which should be paid more attention when explaining clinical tacrolimus-MPA interaction.
format	Articulo Comunicacion
author	Yu, Jian Wang, Chuan-Qiang Fang, Long-Hao Li, Meng Wang, Xiangyang Dai, Lu-Lu Gao, Ya-Jie
author_facet	Yu, Jian Wang, Chuan-Qiang Fang, Long-Hao Li, Meng Wang, Xiangyang Dai, Lu-Lu Gao, Ya-Jie
author_sort	Yu, Jian
title	Tacrolimus (Tacro) strongly inhibits intestinal UDP-glucuronosyltransferase (UGT) 1A8
title_short	Tacrolimus (Tacro) strongly inhibits intestinal UDP-glucuronosyltransferase (UGT) 1A8
title_full	Tacrolimus (Tacro) strongly inhibits intestinal UDP-glucuronosyltransferase (UGT) 1A8
title_fullStr	Tacrolimus (Tacro) strongly inhibits intestinal UDP-glucuronosyltransferase (UGT) 1A8
title_full_unstemmed	Tacrolimus (Tacro) strongly inhibits intestinal UDP-glucuronosyltransferase (UGT) 1A8
title_sort	tacrolimus (tacro) strongly inhibits intestinal udp-glucuronosyltransferase (ugt) 1a8
publishDate	2012
url	http://sedici.unlp.edu.ar/handle/10915/20208 http://www.latamjpharm.org/resumenes/31/4/LAJOP_31_4_2_3.pdf
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bdutipo_str	Repositorios
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Tacrolimus (Tacro) strongly inhibits intestinal UDP-glucuronosyltransferase (UGT) 1A8

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