Tajika Tetsuya, Takahashi Hiroaki, Sakai Yusuke, Fujii Hiroyuki, Isowaki Akiharu, Sakaki Hideyuki
Preclinical Laboratories, Senju Pharmaceutical Co., Ltd., Kobe, Hyogo, Japan.
Xenobiotica. 2010 Aug;40(8):569-77. doi: 10.3109/00498254.2010.490308.
Difluprednate (DFBA; 6alpha,9-difluoro-11beta,17,21-trihydroxy-1,4-pregnadiene-3,20-dione 21-acetate 17-butyrate) is an effective anti-inflammatory agent derived from prednisolone. The present study aimed to evaluate the metabolite profile of DFBA in rabbit ocular tissues after instillation of DFBA ophthalmic emulsion. The high-performance liquid chromatography with radiochemical detection was employed to analyze radioactivity in rabbit ocular tissues that had been instilled with a (3)H-DFBA 0.05% ophthalmic emulsion. At 0.5 and 2 h after instillation, DFBA was not detected in the cornea, aqueous humor, or iris/ciliary body. Instead, 21-deacetylated DFBA (DFB), 17-debutylated DFB (DF), and an unknown metabolite were found. The unknown metabolite was identified as de-17-side chain-glucocorticoid metabolite (DF21C), which is a novel glucocorticoid metabolite formed by the scission of the 17-side chain via an unknown metabolic reaction pathway. The K(i) value of DF21C was 5.6 x 10(-7) mol/L, indicating very weak glucocorticoid receptor binding of DF21C (approximately 1000-fold less than that of DFBA and DFB).
双氟泼尼酯（DFBA；6α,9-二氟-11β,17,21-三羟基-1,4-孕二烯-3,20-二酮21-醋酸酯17-丁酸酯）是一种从泼尼松龙衍生而来的有效抗炎剂。本研究旨在评估DFBA眼用乳剂滴入兔眼组织后的代谢物谱。采用放射化学检测的高效液相色谱法分析用0.05%的(3)H-DFBA眼用乳剂滴注后的兔眼组织中的放射性。滴注后0.5小时和2小时，在角膜、房水或虹膜/睫状体中未检测到DFBA。相反，发现了21-脱乙酰基DFBA（DFB）、17-脱丁酰基DFB（DF）和一种未知代谢物。该未知代谢物被鉴定为去-17-侧链-糖皮质激素代谢物（DF21C），它是一种通过未知代谢反应途径切断17-侧链形成的新型糖皮质激素代谢物。DF21C的K(i)值为5.6×10(-7)mol/L，表明DF21C与糖皮质激素受体的结合非常弱（约比DFBA和DFB低1000倍）。
