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Titolo:
Human CYP2C-mediated stereoselective phenytoin hydroxylation in Japanese: Difference in chiral preference of CYP2C9 and CYP2C19
Autore:
Yasumori, T; Chen, LS; Li, QH; Ueda, M; Tsuzuki, T; Goldstein, JA; Kato, R; Yamazoe, Y;
Indirizzi:
Keio Univ, Sch Med, Dept Pharmacol, Shinjuku Ku, Tokyo 160, Japan Keio Univ Tokyo Japan 160 Dept Pharmacol, Shinjuku Ku, Tokyo 160, Japan Keio Univ, Sch Med, Dept Surg, Shinjuku Ku, Tokyo 160, Japan Keio Univ Tokyo Japan 160 Med, Dept Surg, Shinjuku Ku, Tokyo 160, Japan NIEHS, Res Triangle Pk, NC 27709 USA NIEHS Res Triangle Pk NC USA 27709NIEHS, Res Triangle Pk, NC 27709 USA Tohokuginiv, Fac Pharmaceut Sci, Div Drug Metab & Mol Toxicol, Sendai, Miya Tohoku Univ Sendai Miyagi Japan 98077 g Metab & Mol Toxicol, Sendai, Miya
Titolo Testata:
BIOCHEMICAL PHARMACOLOGY
fascicolo: 11, volume: 57, anno: 1999,
pagine: 1297 - 1303
SICI:
0006-2952(19990601)57:11<1297:HCSPHI>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
S-MEPHENYTOIN 4'-HYDROXYLATION; HUMAN LIVER-MICROSOMES; GENETIC-POLYMORPHISM; POOR METABOLIZERS; TOLBUTAMIDE; CAUCASIANS; INVIVO; DOG; RAT; PHARMACOGENETICS;
Keywords:
phenytoin; cytochrome P450; human liver; drug metabolism; expression in yeast; polymorphism; pharmacogenetics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Yasumori, T Banyutamarmaceut Co Ltd, Dev Res Labs, Drug Metab, 810 Nishijo, Menuma, Sai Banyu Pharmaceut Co Ltd 810 Nishijo Menuma Saitama Japan 3600214
Citazione:
T. Yasumori et al., "Human CYP2C-mediated stereoselective phenytoin hydroxylation in Japanese: Difference in chiral preference of CYP2C9 and CYP2C19", BIOCH PHARM, 57(11), 1999, pp. 1297-1303

Abstract

Regio- and stereoselective hydroxylation of phenytoin was determined in liver microsomes of nine extensive (EM) and three poor metabolizers (PM) of mephenytoin. Hydroxyphenytoins (HPPH) were isolated and quantified after separation into four regio- and stereoisomers. The total rates of microsomal phenytoin 4'- hydroxylation were approximately 3-fold higher than those of 3'-hydroxylation, and not significantly different in EM and PM. Formation of4'-(R)-HPPH was 4.4-fold higher in EM than in PM, whereas no clear differences between EM and PM were detected in the formation of 4'-(S)-, 3'- (R)-,and 3'- (S)-HPPH. Cytochrome P450 (CYP)2C9, expressed in a fission yeast, Schizosaccharomyces pombe, catalyzed the formation of 4'-(R)- and 4'-(S)-HPPH stereoselectively, as observed with EM, in which predominantly 4'- (S)-HPPH was formed. Recombinant CYP2C19 was more stereoselective for 4'-(R)-HPPH formation. These results, in addition to inhibition experiments with anti-human CYP2C antibody, indicate that phenytoin hydroxylation is mainly catalyzed by CYP2C9. Furthermore, CYP2C19 showed limited contribution to phenytoin 4'-hydroxylation with a different chiral preference from CYP2C9. BIOCHEM PHARMACOL 57;11:1297-1303, 1999. (C) 1999 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 19:38:25