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

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)118-124
Number of pages7
JournalDrug Metabolism And Pharmacokinetics
Issue number2
Publication statusPublished - 2013
Externally publishedYes


  • Gastric lesions
  • Liver homogenates
  • Loxoprofen
  • Pharmacokinetics
  • Rat

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)


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