Studies On The Concentration And Pharmacokinetics Of Dexamethasone Following Topical Administration In The Aqueous Fluid And Vitreous Of The Rabbits

Objective To investigate the concentrations and the pharmaco-kinetic parameters of Dexamethasone in the aqueous fluid and vitreous of rabbits after subconjunctival injection,peribulbar injection and single drop. Methods: Sixteen rabbits accepted subconiuntival injection ,sixteen rabbits a-ccepted peribulbar injection,while another sixteen were dropped single withdexamehtasone eye drop(the concentration of Dexamethasone is 0.1%) was dropped single then closed the eyes 10 seconds..The simples of aqueous fl-uid and vitreous in the group of subconjunctival and peribulbar injection were collected at 0.5,1,2,4,510,12,24hours. The simples of aqueous fluid a-nd vitreous were collected at 1/12,1/4,,1/3,1/2,3/4,1,1.5,2hours after single dr-ipping.The concentrations of all the simples were determined by HPLC an-d the pharmacokinetic parameters were analyzed by TOPFIT. Results: the pharmacokinetic parameters were as follows: subconjunctival injections: aqueous: t_1/2(h)=(13.85±1.78), Tmax(h)=(2.00±0.00),Cmax(ug·mL^-1)=(2.63±0.18),AUC_0-t(ug·h·mL^-1)=14.99±0.38,AUC_0-∞(ug·h·mL^-1)=17.05±4.99,MR-T(h)=6.98±0.38, CL/F(ml·min^-1·kg^-1)=2.15±0.15,V_Z/F( L·kg^-1)=2.54±0.14。vitreous: t_1/2(h)=(14.79±1.38), T_max(h)=(2.00±0.00),C_max(ug·mL^-1)=(3.11±0.47),AUC_0-t(ug·h·mL^-1)=15.68±1.31,AUC_0-∞ (ug·h·mL^-1)=16.57±5.22,MR-T(h)=6.99±1.83, CL/F(ml·min^-1·kg^-1)=3.07±0.59,V_Z/F( L·kg^-1)=2.49±0.18。peribulbar,acqueous: t_1/2(h)=(13.89±1.38), T_max(h)=(2.00±0.00),C_max(ug·mL^-1)=(2.58±0.08),AUC_0-t(ug·h·mL^-1)=15.15±0.58,AUC0-∞(ug·h·mL-1)=17.10±5.16,MRT(h)=6.93±0.95,CL/F(ml·min-1·kg-1)=2.19±0.16,VZ/F( L·kg-1)=2.53±0.05。vitreous: t1/2(h)=(14.20±1.18), Tmax(h)=(2.00±0.00),Cmax(ug·mL-1)=(2.68±0.22),AUC0-t(ug·h·mL-1)=15.68±0.76,AUC0-∞(ug·h·mL-1)=18.84±3.14,MR-T(h)=7.47±1.32, CL/F(ml·min-1·kg-1)=2.79±0.25,VZ/F( L·kg-1)=2.62±0.10。drops,acqueous: t1/2(mi-n)=(38.18±1.45), Tmax(min)=(15.00±0.00),Cm-ax(ug·mL-1)=(2.70±0.17),AUC0-t(ug·min·mL-1)= 52.77±0.30,AUC0-∞(ug·h·mL-1)= 57.05±0.74,MRT(min)= 26.88±1.46,CL/F(ml·m-in-1·kg-1)= 43.85±0.59,VZ/F( L·kg-1)=2.41±0.07. Conclusion:The maxium dexamethasonedensity in the acqueous fluid is near in the drop and subconiuntival injecti-on groups, but the time of working is longer in the group of subconjunctiv-al injection.Several dripping can replace single subconjunctival injection. Subconjunctival injection is better than peribulbar injection.