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 journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)118-124
Number of pages7
JournalDrug Metabolism and Pharmacokinetics
Volume28
Issue number2
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Pharmacokinetics
Alcohols
Prodrugs
Anti-Inflammatory Agents
fluoro-loxoprofen
loxoprofen
Pharmaceutical Preparations
Intravenous Administration
Oral Administration
Stomach
Liver
In Vitro Techniques

Keywords

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

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Pharmaceutical Science

Cite this

Comparison of pharmacokinetics between loxoprofen and its derivative with lower ulcerogenic activity, fluoro-loxoprofen. / Yamakawa, Naoki; Suemasu, Shintaro; Watanabe, Hiroshi; Tahara, Kayoko; Tanaka, Ken ichiro; Okamoto, Yoshinari; Ohtsuka, Masami; Maruyama, Toru; Mizushima, Tohru.

In: Drug Metabolism and Pharmacokinetics, Vol. 28, No. 2, 2013, p. 118-124.

Research output: Contribution to journalArticle

Yamakawa, N, Suemasu, S, Watanabe, H, Tahara, K, Tanaka, KI, Okamoto, Y, Ohtsuka, M, Maruyama, T & Mizushima, T 2013, 'Comparison of pharmacokinetics between loxoprofen and its derivative with lower ulcerogenic activity, fluoro-loxoprofen', Drug Metabolism and Pharmacokinetics, vol. 28, no. 2, pp. 118-124. https://doi.org/10.2133/dmpk.DMPK-12-RG-050
Yamakawa, Naoki ; Suemasu, Shintaro ; Watanabe, Hiroshi ; Tahara, Kayoko ; Tanaka, Ken ichiro ; Okamoto, Yoshinari ; Ohtsuka, Masami ; Maruyama, Toru ; Mizushima, Tohru. / Comparison of pharmacokinetics between loxoprofen and its derivative with lower ulcerogenic activity, fluoro-loxoprofen. In: Drug Metabolism and Pharmacokinetics. 2013 ; Vol. 28, No. 2. pp. 118-124.
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