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ME Mahmoud, M Cooney, E de Juan; Multi-Dose Efficacy Study of Genistein in Laser-Induced Choroidal Neovascularization in Primates . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1283.
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Purpose: Previous studies demonstrated that genistein ameliorated choroidal neovascularization (CNV) in experimental animals by inhibiting phosphotyrosine kinase. We studied the effect of multi-dose oral administration of genistein on laser induced CNV in primates. Methods: Four primates received laser photocoagulation in 1 eye each to serve as control eyes. Ten argon laser burns were applied in a grid fashion to the posterior pole of the control eyes using a 100 micron spot size, 0.1 sec duration, and 750 mWatts.The development of CNV in the control eye after photocoagulation was followed angiographically for 3 weeks. At the conclusion of the control eye portion of the experiment, 2 of the primates received oral doses of pure synthetic genistein (99%) at 25 mg/kg for 3 days before to laser photocoagulation in the study eye and daily for 3 weeks thereafter. The remaining 2 primates received oral genistein at 100 mg/kg according to the same schedule. For both groups, genistein was given in a banana, twice daily. The development of CNV in the treatment eye after photocoagulation was followed angiographically for 3 weeks. Blood was collected weekly and plasma free genistein concentration was measured using HPLC. Fluorescein angiograms were interpreted by two masked observers Results: Pooled data analysis showed a strong trend for a reduction of CNV development after laser photocoagulation at the 3- week timepoint in the eyes of primates receiving genistein 25 mg/kg compared with the control eyes (p=0.055). There was no significant difference in the development of CNV after laser photocoagulation in the eyes of primates receiving genistein 100 mg/kg (p=1.00). Genistein 100 mg/kg dose resulted in a significantly lower plasma level of free genistein (0.29 ± 0.065 ug/ml) than did the 25 mg/kg dose (0.66 ± 0.15 ug/ml) (p< 0.001). Genistein decayed in the plasma of primate exhibiting 2 compartmental open model. The bioavailability of the 25 mg/kg dose was 21.6% whereas the bioavailability of 100 mg/kg dose was 2.36 %. Conclusion: The efficacy of genistein in inhibiting the development of CNV appears to be directly related to the level of plasma free genistein. The bioavailability of genistein decreased as the dose increased.
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