Metabolic profiles of difluprednate in rabbit ocular tissues after instillation of difluprednate ophthalmic emulsion.

Article Details

Citation

Copy to clipboard

Tajika T, Takahashi H, Sakai Y, Fujii H, Isowaki A, Sakaki H

Metabolic profiles of difluprednate in rabbit ocular tissues after instillation of difluprednate ophthalmic emulsion.

Xenobiotica. 2010 Aug;40(8):569-77. doi: 10.3109/00498254.2010.490308.

PubMed ID

20509750 [ View in PubMed

]

Abstract

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).

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Difluprednate	Glucocorticoid receptor	Protein	Humans	Yes	Agonist	Details