Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
In vitro metabolism and interaction of cilostazol with human hepatic cytochrome P450 isoforms
Autore:
Abbas, R; Chow, CP; Browder, NJ; Thacker, D; Bramer, SL; Fu, CJ; Forbes, W; Odomi, M; Flockhart, DA;
Indirizzi:
Otsuka Amer Pharmaceut Inc, Rockville, MD 20850 USA Otsuka Amer PharmaceutInc Rockville MD USA 20850 Rockville, MD 20850 USA Purdue Pharma LP, Dept Drug Safety Evaluat, Ardsley, NY 10502 USA Purdue Pharma LP Ardsley NY USA 10502 fety Evaluat, Ardsley, NY 10502 USA Georgetown Univ, Med Ctr, Dept Med, Div Clin Pharmacol, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 armacol, Washington, DC 20007 USA Kansas City Analyt Serv, Kansas City, KS 66216 USA Kansas City Analyt Serv Kansas City KS USA 66216 ansas City, KS 66216 USA Otsuka Pharmaceut Co Ltd, Tokushima Res Inst, Tokushima 77101, Japan Otsuka Pharmaceut Co Ltd Tokushima Japan 77101 t, Tokushima 77101, Japan
Titolo Testata:
HUMAN & EXPERIMENTAL TOXICOLOGY
fascicolo: 3, volume: 19, anno: 2000,
pagine: 178 - 184
SICI:
0960-3271(200003)19:3<178:IVMAIO>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
MICROSOMES; INHIBITOR;
Keywords:
cilostazol; in vitro; metabolism; CYP450; isoforms; interaction;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
12
Recensione:
Indirizzi per estratti:
Indirizzo: Abbas, R Otsuka Amer Pharmaceut Inc, 2440 Res Blvd, Rockville, MD 20850 USA Otsuka Amer Pharmaceut Inc 2440 Res Blvd Rockville MD USA 20850 A
Citazione:
R. Abbas et al., "In vitro metabolism and interaction of cilostazol with human hepatic cytochrome P450 isoforms", HUM EXP TOX, 19(3), 2000, pp. 178-184

Abstract

1 Cilostazol (OPC-13013) undergoes extensive hepatic metabolism. The hydroxylation of the quinone moiety of cilostazol to OPC-13326 was the predominant route in all the liver preparations studies. The hydroxylation of the hexane moiety to OPC-13217 was the second most predominant route in vitro.2 Ketoconazole (1 mu M) was the most potent inhibitor of both quinone and hexane hydroxylation. both the CYP2D6 inhibitor quinidine (0.1 mu M) and the CYP2C19 inhibitor omeprazole (10 mu M) failed to consistently inhibit metabolism of cilostazol via either of these two predominant routes.3 Data obtained from a bank of pre-characterized human liver microsomes demonstrated a stronger correlation (r(2)=0.68, P < 0.01) between metabolism of cilostazol to OPC-13326 and metabolism of felodipine, a CYP3A probe, that with probes for any other isoform. Cimetidine demonstrated concentration-dependent competitive inhibition of the metabolism of cilostazol by both routes.4 Kinetic data demonstrated a Km value of 101 mu M for cilostazol, suggesting a relatively low affinity of cilostazol for CYP3A. While recombinant CYP1A2, CYP2D6 and CYP2C19 were also able to catalyze formation of specific cilostazol metabolites, they did not appear to contribute significantly to cilostazol metabolism in whole human liver microsomes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 06:25:28