Absorption, distribution, metabolism and excretion of loxoprofen after dermal application of loxoprofen gel to rats. (November 2014)

• Record Type: Journal Article
• Authors: Sawamura, Ryoko; Kazui, Miho; Kurihara, Atsushi; Izumi, Takashi
• Is Part Of: Xenobiotica. Volume 44:Number 11(2014:Nov.)
• Page Start: 1026
• Page End: 1038
• Publication Date: 2014-11
• Subjects: Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.3109/00498254.2014.926571
• Languages: English
• ISSNs: 0049-8254

Abstract

<abstract> <title>Abstract</title> <p>1. Loxoprofen (LX), is a prodrug of the pharmacologically active form, <italic>trans</italic>-alcohol metabolite (<italic>trans</italic>-OH form), which shows very potent analgesic effect. In this study, the pharmacokinetics and metabolism of [<sup>14</sup>C]LX-derived radioactivity after dermal application of [<sup>14</sup>C]LX gel (LX-G) to rats were evaluated.</p> <p>2. The area under concentration-time curve (AUC<sub>0–∞</sub>) of radioactivity in the plasma after the dermal application was 13.6% of that of the oral administration (<italic>p</italic> < 0.05).</p> <p>3. After the dermal application, the radioactivity remained in the skin and skeletal muscle at the treated site for 168 h, whereas the AUC<sub>0–168 h</sub> of the radioactivity concentration in every tissue examined except the treated site was statistically lower than that after the oral administration (<italic>p</italic> < 0.05).</p> <p>4. The <italic>trans</italic>-OH form was observed at high levels in the treated skin site at 0.5 h. Metabolite profiles in plasma, non-treated skin site and urine after the dermal application were comparable with those after the oral administration.</p> <p>5. Renal excretion was the main route of elimination after the dermal application.</p> <p>6. In conclusion, compared to the oral administration, the dermal application of [<sup>14</sup>C]LX-G showed lower systemic and tissue exposure with higher exposure in the therapeutic target site. The radioactivity revealed similar metabolite profiles in both administration routes.</p> </abstract>