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Titolo:
Oxidation of ranitidine by isozymes of flavin-containing monooxygenase andcytochrome P450
Autore:
Chung, WG; Park, CS; Roh, HK; Lee, WK; Cha, YN;
Indirizzi:
Inha Univ, Coll Med, Dept Pharmacol, Inchon 402751, South Korea Inha UnivInchon South Korea 402751 harmacol, Inchon 402751, South Korea Inha Univ, Coll Med, Med Toxicol Res Ctr, Inchon 402751, South Korea Inha Univ Inchon South Korea 402751 Res Ctr, Inchon 402751, South Korea Inha Univ, Coll Med, Dept Internal Med, Inchon 402751, South Korea Inha Univ Inchon South Korea 402751 rnal Med, Inchon 402751, South Korea Gachon Med Sch, Gil Med Ctr, Dept Gen Surg, Inchon 405760, South Korea Gachon Med Sch Inchon South Korea 405760 urg, Inchon 405760, South Korea
Titolo Testata:
JAPANESE JOURNAL OF PHARMACOLOGY
fascicolo: 2, volume: 84, anno: 2000,
pagine: 213 - 220
SICI:
0021-5198(200010)84:2<213:OORBIO>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
PYRROLIZIDINE ALKALOID SENECIONINE; PERFORMANCE LIQUID-CHROMATOGRAPHY; HEPATIC MICROSOMES; LIVER-MICROSOMES; DRUG-METABOLISM; RAT; SPIRONOLACTONE; ANTAGONISTS; CIMETIDINE; URINE;
Keywords:
ranitidine N-oxide; ranitidine S-oxide; desmethylranitidine; flavin-containing monooxygenase probe; cytochrome P450;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Cha, YN Inha Univ, Coll Med, Dept Pharmacol, Inchon 402751, South Korea Inha Univ Inchon South Korea 402751 , Inchon 402751, South Korea
Citazione:
W.G. Chung et al., "Oxidation of ranitidine by isozymes of flavin-containing monooxygenase andcytochrome P450", JPN J PHARM, 84(2), 2000, pp. 213-220

Abstract

Rat and human liver microsomes oxidized ranitidine to its N-oxide (66-76%)and S-oxide (13 - 18%) and desmethylranitidine (12 - 16%). N- and S-oxidations of ranitidine were inhibited by metimazole [flavin-containing monooxygenase (FMO) inhibitor] to 96-97% and 71-85%, respectively, and desmethylation of ranitidine was inhibited by SKF525A [cytochrome P450 (CYP) inhibitor]by 71-95%. Recombinant FMO isozymes like FMO1, FMO2, FMO3 and FMO5 produced 39, 79, 2180 and 4 ranitinine N-oxide and 45, 0, 580 and 280 ranitinine S-oxide pmol.min(-1).nmol(-1) FMO, respectively. Desmethyranitinine was not produced by recombinant FMOs. Production of desmethylranitidine by rat and human liver microsomes was inhibited by tranylcypromine, alpha -naphthoflavon and quinidine, which are known to inhibit CYP2C19, 1A2 and 2D6, respectively. FMO3, the major form in adult liver, produced both ranitidine N- and S-oxides at a 4 to 1 ratio. FMO1, expressed primarily in human kidney, was 55- and 13-fold less efficient than the hepatic FMO3 in producing ranitidine N- and S-oxides, respectively. FM02 and FMO5, although expressed slightlyin human liver, kidney and lung, were not efficient producers of ranitidine N- and S-oxides. Thus, urinary contents of ranitidine N-oxide can be usedas the in vivo probe to determine the hepatic FMO3 activity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/01/20 alle ore 01:01:53