Changes of intraocular drug concentration and pharmacokinetics of bevacizumab with annexin A5-associated liposome topically applied in the rabbit eyes / 中华眼底病杂志

ABSTRACT

Objectives To explore intraocular drug concentration changes and the pharmacokinetics after topically applied of bevacizumab with armexin A5-associated liposome on rabbit eyes.Methods A total of 105 healthy New Zealand white rabbits were selected and divided randomly into 3 groups (group A,B and C),and each group had 35 rats.Bevacizumab with annexin A5-associated liposome,bevacizumab liposome and bevacizumab were topically applied 50 μl respectively on right eyes of rabbits in group A,B and C,respectively.Aqueous,vitreous body and retina/choroid were obtained at 5,15,30 minutes and 1,2,4,8 hours and the free bevacizumab concentrations in these ocular tissues were measured by ELISA (enzyme linked immunosorbent assay).DAS 2.1.1 software was used to fit the pharmacokinetic parameters.Results The peak drug concentrations in aqueous humor of the eyes in group A,B,C were at 15 minutes after topical administration and the difference was statistically significant (F=301.061,P＜ 0.01).The peak drug concentrations in vitreous of the eyes in the group A,B,C were at 2 hours after topical administration and the difference was statistically significant (F=885.997,P＜ 0.01).The peak drug concentrations in retina/choroid of the eyes in the group A,B,C were at 1 hour after topical administration and the difference was statistically significant (F=644.908,P＜0.01).Least significant difference pair-wise test found that the drug concentrations in aqueous humor,vitreous and retina/choroid of group A was higher than that of the group B and C respectively (P＜ 0.05),while that of the group B and C had no significant different (P＞ 0.05).Pharmacokinetic fitting analysis found that the half-life (t1/2) of bevacizumab in aqueous humor were 1.14,1.29,1.29 hours,the distribution t1/2 were 1.40,1.50,1.42 hours and the eliminated t1/2 were 2.62,2.84,2.73 hours in vitreous,the distribution t1/2 were 2.61,2.99,2.70hours and the eliminated t％ were 2.61,2.99,2.70 hours in retina/choroid respectively for the 3 groups.Changes of bevacizumab concentration in aqueous humor of rabbit eyes for 3 groups was complied with one compartment model,and that in vitreous body and retina/choroid complied with two compartment model.Conclusions Topically applied annexin A5-associated liposome has higher ocular concentrations of bevacizumab than those of controls.Changes of bevacizumab concentration in aqueous humor of rabbit eyes was complied with one compartment model,and that in vitreous body and retina/choroid complied with two compartment model.