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Ken Mizuno, Takashi Koide, Naohiro Saito, Mikio Fujii, Miyuki Nagahara, Atsuo Tomidokoro, Yasuhiro Tamaki, Makoto Araie; Topical Nipradilol: Effects on Optic Nerve Head Circulation in Humans and Periocular Distribution in Monkeys. Invest. Ophthalmol. Vis. Sci. 2002;43(10):3243-3250.
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purpose. To investigate the effects of topical nipradilol on blood velocity in the optic nerve head (ONH) in normal humans and the ocular and periocular distribution of topically instilled nipradilol in monkeys.
methods. In normal humans, 0.25% nipradilol was instilled in one eye and vehicle in the other twice daily for 7 days, and blood velocity in the ONH was measured by the laser speckle method. In monkeys, after a single instillation of 1% [14C]nipradilol in one eye, distribution of radioactivity was evaluated by whole-head autoradiography.
results. Twice-daily 7-day instillation of nipradilol temporarily but significantly increased human ONH blood velocity, in the ipsilateral eye only (P = 0.005), independent of a reduction in the intraocular pressure. In monkeys, equivalent nipradilol concentration in the periocular tissue around the optic nerve insertion was higher on the ipsilateral side than on the contralateral side (140 ± 25 ng/g and 42 ± 10 ng/g, P = 0.022, n = 5). Radioactivity was higher in the periocular tissue behind the equator than around the optic nerve insertion on the ipsilateral side (P = 0.004), but not on the contralateral side. The equivalent nipradilol concentration in the ipsilateral posterior retina-choroid was 636 ± 92 ng/g, which was significantly higher than that on the contralateral control side (521 ± 92 ng/g, P < 0.001).
conclusions. The ipsilateral increase in ONH blood velocity induced by topical nipradilol in humans was attributed to drug that penetrated locally. Whole-head autoradiographic study suggests that topically instilled nipradilol can rapidly reach the posterior periocular tissue at pharmacologic concentrations.
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