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

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          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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          Author and article information

          Journal
          Drug Metab. Pharmacokinet.
          Drug metabolism and pharmacokinetics
          1880-0920
          1347-4367
          2013
          : 28
          : 2
          Affiliations
          [1 ] Department of Analytical Chemistry, Faculty of Pharmacy, Keio University, Tokyo, Japan.
          Article
          DN/JST.JSTAGE/dmpk/DMPK-12-RG-050
          22892443
          970f743f-9cab-44ab-be30-0d17b2d20e87
          History

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