Comparison of pharmacokinetics between loxoprofen and its derivative with lower ulcerogenic activity, fluoro-loxoprofen

Naoki Yamakawa, Shintaro Suemasu, Hiroshi Watanabe, Kayoko Tahara, Ken ichiro Tanaka, Yoshinari Okamoto, Masami Ohtsuka, Toru Maruyama, Tohru Mizushima

研究成果: Article査読

14 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)118-124
ページ数7
ジャーナルDrug Metabolism And Pharmacokinetics
28
2
DOI
出版ステータスPublished - 2013
外部発表はい

ASJC Scopus subject areas

  • 薬理学
  • 薬科学
  • 薬理学(医学)

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