Kenji Kashiwagi, Yoko Iizuka and Shigeo Tsukahara
Department of Ophthalmology, Yamanashi Medical University, Tamaho, Yamanashi
409 - 3898, Japan
Abstract: The intraocular metabolism of isopropyl unoprostone,
a novel prostaglandin-related anti-glaucoma compound, was investigated using
pigmented rabbits to clarify which metabolites are involved in actions in
the eye. Tritium-labeled isopropyl unoprostone eyedrops were administered.
The cornea, aqueous humor, iris, ciliary body and retina were then collected
at 5, 15 or 30 min or at 2, 6 or 12 h after instillation. Isopropyl unoprostone
and its metabolites were fractionated using high-performance liquid chromatography,
and the radioactivity of each fraction was measured. Unmetabolized isopropyl
unoprostone was never detected in any sample at any time point. In the cornea,
only the de-esterificated metabolite, M1, and the further metabolized compound,
M2, were detected; and the concentrations of these metabolites decreased
with time. In the aqueous humor, M1, M2 and another metabolite, M3, were
detected, with peak concentrations of M1 at 30 min and M2 at 2 h. The iris
and ciliary body showed a similar metabolism with peak concentrations of
M1 and M2 at 30 min. In the aqueous humor, iris and ciliary body, M2 was
the dominant metabolite from 30 min. In the retina, only total radioactivity
was detected. These results indicate that the main metabolites involved
in actions in the eye are M1 and M2.
Keywords: Isopropyl unoprostone, Prostaglandin, Glaucoma, Metabolism,
Esterase