TY - JOUR T1 - Disposition and Metabolism of a Novel Prostanoid Antiglaucoma Medication, Tafluprost, Following Ocular Administration to Rats JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1622 LP - 1634 DO - 10.1124/dmd.108.024885 VL - 37 IS - 8 AU - Y. Fukano AU - K. Kawazu Y1 - 2009/08/01 UR - http://dmd.aspetjournals.org/content/37/8/1622.abstract N2 - The disposition and metabolism of tafluprost, an ester prodrug of the 15,15-difluoro-prostaglandin F2α antiglaucoma agent, have been studied in rats after ocular administration. Radioactivity was absorbed very rapidly into the eye and systemic circulation after a single ocular dose of 0.005% [3H]tafluprost ophthalmic solution, with maximum levels in plasma and most eye tissues occurring within 15 min. The absorption ratio of radioactivity was approximately 75%, suggesting the high availability of ocular administration of tafluprost. Approximately 10% of the dose was present in cornea at this time, and radioactivity concentrations in this tissue exceeded those in aqueous humor and iris/ciliary body throughout the 24-h study period. After repeated daily ocular doses, radioactivity levels remained greatest in cornea, followed by iris/ciliary body that replaced aqueous humor as the eye tissue containing the second highest radioactivity concentration. In female rats, radioactivity was excreted equally between urine and feces after a single ocular dose, whereas in male rats more was excreted in feces, reflecting the greater biliary excretion in males rats (50% dose) compared with females rats (33% dose). Tafluprost was extensively metabolized in the rat, such that intact prodrug was not detected in plasma, tissues, or excreta by radio-high-performance liquid chromatography. On the other hand, the active moiety, tafluprost acid, was the only noteworthy radioactive component in cornea, aqueous humor, and iris/ciliary body for at least 8 h after the ocular dose, and it was also a major plasma metabolite in early time points. The gender differences in conjugation reactions resulted in the differences in the excretion. ER -