Intraocular Pharmacokinetic Following Injection Of Triamcinolone Acetonide Via Posterior Sub-tenon In Rabbit Eyes

Objective:To investigate the concentrations and the pharmacokinetic parameters of triamcinolone acetonide in retina and vitreous of rabbits after posterior sub-tenon injection of TA, and provide the experimental basis for clinical applications.Methods: The left eyes of 32 rabbits received a posterior sub-tenon injection of 20 mg TA (0.1mL) suspension as the experimental eyes(B group), and the fellow eyes received 0.1mL normal saline solution as the control eyes(A group). The rabbits were divided into eight subgroups according to the time after drug injection(1,3,7day,2,3,4,6,8week). The intraocular pressure (IOP) and slit-lamp examination were recorded before and after drug injection to evaluate the safety of a posterior sub-tenon injection of TA. The rabbits were killed at eight different time points following posterior sub-tenon injection of TA respectively and the retina and vitreous specimens were collected immediately. TA concentration were detected by high performance liquid chromatography (HPLC) and the pharmacokinetics analysis of drug was performed. 1μg/mL prednisolone-methanol solution was as reference solution.Results: The vitreous regression equation of TA /prednisolone peak area(Y) and TA/prednis -olone concentration(X) was Y= 0.4329X +0.5397, presenting a good linear correlation between them (R2=0.9951, P<0.05).The retina regression equation of TA /prednisolone peak area(Y) and TA/prednisolone concentration(X) was Y=0.4205X+1.9377, presenting a good linear correlation between them (R2=0.9986, P<0.05).TA concentration were (0.35±0.07)μg·mL-1,(0.86±0.11)μg. g-1in vitreous and retina at 1 day following posterior sub-tenon injection of TA, respectively. And the maximal concentration of vitreous and retina were (1.91±0.13)μg·mL-1,(2.36±0.14)μg.g-1 at 14 days and after that showed a declining trend till 56 days. The pharmacokinetic parameters were as follows:Vitreous: t?=(8.51±1.34)d, T(peak)= (14.52±1.06)d, Cmax=(1.94±0.67)μg.mL-1, AUC=(33.14±0.72)μg.day.mL-1;Retina: t?=(15.42±1.45)d,T(peak)= (11.37±1.95)d, Cmax=(2.68±0.83)μg.g-1,AUC= (40.78±1.01)μg.day.g-1. No any ocular complication was found throughout the studying duration. No significant alteration was found in IOP between before and after poster -ior sub-tenon injection of TA or TA group and normal saline solution group(P>0.05). Conclusion:1. The drug can be permeated into vitreous cavity via eyeball wall after a posterior sub-tenon injection of TA in rabbit eyes.2. The pharmacokinetic parameters were as follows: Vitreous:t?= (8.51±1.34)d, T(peak)= (14.52±1.06)d, Cmax= (1.94±0.67)μg.mL-1, AUC= (33.14±0.72)μg.day.mL-1;Retina: t? = (15.42±1.45)d, T(peak)= (11.37±1.95)d, Cmax= (2. 68±0.83)μg.g-1, AUC=(40.78±1.01)μg. day.g-1.3. The effective drug concentration can be retained in the vitreous cavity and retina after a posterior sub-tenon injection of TA in rabbit eyes.