Interakce nabumetonu s cytochromy P450 in vitro: srovnání u člověka a prasete

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F07%3A00004264" target="_blank" >RIV/61989592:15110/07:00004264 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

INTERACTION OF NABUMETONE WITH CYTOCHROMES P450 IN VITRO:COMPARISON OF THE MAN AND PIG

Popis výsledku v původním jazyce

Nabumetone (4-(6-methoxy-2- naphtyl)-butan-2-one) is a nonsteroidal anti-infl ammatory prodrug, clinically used mainly for treatment of osteoarthritis or rheumatoid arthritis to reduce pain and infl ammation. It undergoes rapid and extensive fi rst-passmetabolism in liver to form the main circulating active metabolite 6-methoxy-2-naphthylacetic acid (6-MNA), which is a potent inhibitor of cyclooxygenase (COX-2). Three main metabolic pathways of nabumetone were described: O-demethylation, reduction of ketone to an alcohol, and an oxidative cleavage of the side-chain1. Possible interactions of nabumetone with liver microsomal cytochromes P450 (CYPs, which are often responsible not only for drug metabolism, but also for unwanted eff ects such an enzyme inhibition or induction2) are studied here at the level of human and pig liver microsomes. To prove the suitability of pig as an experimental model for following of metabolism and pharmacokinetics of drugs we compared the inhibition of a

Název v anglickém jazyce

INTERACTION OF NABUMETONE WITH CYTOCHROMES P450 IN VITRO:COMPARISON OF THE MAN AND PIG

Popis výsledku anglicky

Nabumetone (4-(6-methoxy-2- naphtyl)-butan-2-one) is a nonsteroidal anti-infl ammatory prodrug, clinically used mainly for treatment of osteoarthritis or rheumatoid arthritis to reduce pain and infl ammation. It undergoes rapid and extensive fi rst-passmetabolism in liver to form the main circulating active metabolite 6-methoxy-2-naphthylacetic acid (6-MNA), which is a potent inhibitor of cyclooxygenase (COX-2). Three main metabolic pathways of nabumetone were described: O-demethylation, reduction of ketone to an alcohol, and an oxidative cleavage of the side-chain1. Possible interactions of nabumetone with liver microsomal cytochromes P450 (CYPs, which are often responsible not only for drug metabolism, but also for unwanted eff ects such an enzyme inhibition or induction2) are studied here at the level of human and pig liver microsomes. To prove the suitability of pig as an experimental model for following of metabolism and pharmacokinetics of drugs we compared the inhibition of a

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

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Projekt

<a href="/cs/project/1P05OC050" target="_blank" >1P05OC050: Porcinní biotransformační enzymy</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2007

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Biomedical Papers

ISSN

1213-8118

e-ISSN

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Svazek periodika

151

Číslo periodika v rámci svazku

S1

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

2

Strana od-do

53-54

Kód UT WoS článku

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EID výsledku v databázi Scopus

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