Comparison of pharmacokinetics between loxoprofen and its derivative with lower ulcerogenic activity, fluoro-loxoprofen.
Drug Metab Pharmacokinet
; 28(2): 118-24, 2013.
Article
em En
| MEDLINE
| ID: mdl-22892443
ABSTRACT
We recently reported that, compared to loxoprofen (LOX, an non-steroidal anti-inflammatory drug), the LOX derivative fluoro-loxoprofen (F-LOX) is less ulcerogenic but has similar anti-inflammatory activity. Our previous in vitro studies suggested that both LOX and F-LOX are pro-drugs, the active metabolites of which are their trans-alcohol forms. In this study, we compared the pharmacokinetics of F-LOX and LOX in rats. Overall, the pharmacokinetic characteristics of F-LOX, including the formation of metabolites in vivo and in vitro, were comparable to those of LOX. However, F-LOX disappeared from the plasma more rapidly than LOX, which could potentially explain its lower ulcerogenicity. However, we showed that F-LOX produced fewer gastric lesions than LOX, even when a higher plasma concentration of F-LOX was maintained. Similar to LOX, F-LOX was readily metabolized to its trans- and cis-alcohol forms, with a higher level of the trans-alcohol form being observed after oral or intravenous administration of the drug. The preferential formation of the trans-alcohol form was also observed after incubation of F-LOX with rat liver homogenates in vitro. These results suggest that, similar to LOX, F-LOX acts as a pro-drug and that there is a metabolic system that selectively produces its active metabolite.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenilpropionatos
/
Úlcera Gástrica
/
Pró-Fármacos
/
Anti-Inflamatórios não Esteroides
Limite:
Animals
Idioma:
En
Revista:
Drug Metab Pharmacokinet
Assunto da revista:
FARMACOLOGIA
/
METABOLISMO
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Japão