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Pharmacokinetics of a long-lasting anti-VEGF fusion protein in rabbit.
Experimental Eye Research 2012 April
Conbercept(KH902), a recombinant fusion protein in clinical trial II/III, shows good potential to treat the neovascular age-related macular degeneration (AMD). This investigation evaluated its ocular pharmacokinetics and pharmacodynamic profile in rabbits following intravitreal administration (IVT). Rabbits (n = 120) received single bilateral conbercept IVT administration or single IV administration. Conbercept concentrations in ocular tissues and serum were measured after dosing. VEGF concentration was also measured simultaneously. The results showed that conbercept rapidly distributed from vitreous into targeted tissues and lasted over 81 days. Clearance in ocular tissues was parallel and exhibited a terminal half of 2.5-4.2 days. The drug exposure in the retina was 1/4 to 1/5 of that in vitreous. Serum conbercept concentrations after IVT dosing were low and bioavailability was approximately 44%. And single intravitreal injection induced that ocular VEGF concentration declined over 60 days and serum VEGF concentration decreased for a short time but rebounded to higher level than baseline later. All these indicated conbercept good pharmacokinetic profile in rabbits, with good ocular tropism and systemic tolerance. Combined with the efficacy data from our earlier in vitro and in vivo studies, it should have a promising clinical application for AMD treatment.
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