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Titolo:
Use of cloned and expressed human UDP-glucuronosyltransferases for the assessment of human drug conjugation and identification of potential drug interactions
Autore:
Ethell, BT; Beaumont, K; Rance, DJ; Burchell, B;
Indirizzi:
Univ Dundee, Ninewells Hosp & Med Sch, Dept Mol & Cellular Pathol, Dundee DD1 9SY, Scotland Univ Dundee Dundee Scotland DD1 9SY lar Pathol, Dundee DD1 9SY, Scotland Pfizer Cent Res, Project Management Dept, Sandwich, Kent, England Pfizer Cent Res Sandwich Kent England ment Dept, Sandwich, Kent, England Pfizer Cent Res, Dept Drug Metab, Sandwich, Kent, England Pfizer Cent ResSandwich Kent England rug Metab, Sandwich, Kent, England
Titolo Testata:
DRUG METABOLISM AND DISPOSITION
fascicolo: 1, volume: 29, anno: 2001,
pagine: 48 - 53
SICI:
0090-9556(200101)29:1<48:UOCAEH>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
XENOBIOTIC GLUCURONIDATION; METABOLIZING-ENZYMES; STABLE EXPRESSION; BILIRUBIN; CATALYZES; CLONING; SPECIFICITY; PROPOFOL; ACID;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Ethell, BT Univ Dundee, Ninewells Hosp & Med Sch, Dept Mol & Cellular Pathol, Dundee DD1 9SY, Scotland Univ Dundee Dundee Scotland DD1 9SY Dundee DD1 9SY, Scotland
Citazione:
B.T. Ethell et al., "Use of cloned and expressed human UDP-glucuronosyltransferases for the assessment of human drug conjugation and identification of potential drug interactions", DRUG META D, 29(1), 2001, pp. 48-53

Abstract

Glucuronidation is an important pathway for human drug metabolism. Four cloned and expressed human UDP-glucuronosyltransferases (UGT1A1, UGT1A6, UGT1A9, and UGT2B15) were used to screen a series of three potential drug substrates differing only in position of the phenol moiety. The meta and para phenols, UK-156,037 and UK-157,147, were found to be substrates for UGT1A1 with K-m values of 256 and 105 muM, respectively. The ortho phenol UK-157,261was glucuronidated predominantly by UGT1A9 with a K-m of 45 muM. The latter K-m compares favorably with the known UGT1A9 substrate propofol (K-m = 200 muM). In a series of competition experiments, UK-157,261 was shown to inhibit the glucuronidation of propofol by UGT1A9 with a K-i value of 65 muM. This result indicates that even the most potent of these compounds is extremely unlikely to interact in the clinic with the glucuronidation of propofol. This study shows the utility of the expressed human UDP-glucuronosyltransferases in determining substrate structure-activity relationships and potential drug-drug interactions.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/09/20 alle ore 02:18:56