PT  - JOURNAL ARTICLE
AU  - K Higaki
AU  - K Kamata
AU  - M Takeuchi
AU  - K Inazawa
AU  - T Chikai
AU  - T Hamaguchi
AU  - T Yukawa
AU  - K Kadono
AU  - S Kawahara
AU  - M Nakano
TI  - Ocular absorption, distribution, and systemic absorption of a novel antiglaucoma medication, prostaglandin derivative, in male white rabbits.
DP  - 1995 Jan 01
TA  - Drug Metabolism and Disposition
PG  - 35--43
VI  - 23
IP  - 1
4099  - http://dmd.aspetjournals.org/content/23/1/35.short
4100  - http://dmd.aspetjournals.org/content/23/1/35.full
SO  - Drug Metab Dispos1995 Jan 01; 23
AB  - A prostaglandin derivative, (5Z,9 alpha,11 alpha,13E)-9,11-dihydroxyprosta- 5,13-dienoic acid sodium salt (S-1033), that lowers intraocular pressure with little adverse effect, may have clinical value in the treatment of glaucoma. After [14C]S-1033 (0.2% solution) was instilled into the eye of a white rabbit, radioactivity and S-1033 appeared in systemic plasma so rapidly (tmax, 5 min) and S-1033 was eliminated very rapidly with half-lives of 2.8 and 11.0 min at alpha- and beta-phases, respectively. The metabolite, M-1, [1R-[1 alpha,2 beta-(1E),3 alpha,5 alpha]]-3,5-dihydroxy-2-(1- octenyl)-cyclopentanepropanoic acid (tetranor-S-1033), appeared in plasma very rapidly (tmax, 5 min), suggesting that a fast metabolism was a major factor in the rapid elimination of S-1033 from plasma. The values for the ratios of the area under the curve of ocular instillation to intravenous administration for radioactivity and S-1033 were 1.01 and 0.52, respectively, indicating that more than half of the S-1033 instilled was transported into the systemic circulation. To clarify the contributing pathway of the massive and rapid systemic absorption of S-1033 after topical dosing, plasma levels of S-1033 were investigated after instillation to rabbits in which the nasolacrimal ducts were occluded. Plasma concentrations of S-1033 were slightly higher than those in intact rabbits, suggesting that conjunctiva would be as important as nasal mucosae for the systemic absorption under the physiological condition. As for the intraocular distribution, the highest levels of radioactivity were found in the cornea, conjunctiva, and anterior sclera.(ABSTRACT TRUNCATED AT 250 WORDS)