Pharmacokinetics Of Tetrandrine In Aqueous Humor Of Rabbit Following Subconjunctival Administration

ObjectiveThe aim of the study was to investigate the pharmacokinetic parameters of the tetrandrine following subconjunctival administration and whether it can penetrate blood-aqueous barrier or not.Method16 rabbits were given subconjunctival administration by a single dose of tetrandrine 5 mg,the concentration of tetrandrine in aqueous humor at various time(0.25,0.5,1,2.5,3,4.5,8h)was determined by HPLC,and the parmacokinetic parameters were analyzed by DSA2.1.1.ResultIn HPLC assay of tetrandrine,under those experimental conditions,tetrandrine had a good relationship between the concentration and peak area in the rang of (0.025-5.0)mg·L^-1,(r=0.9973).There are high concentration of tetrandrine in aqueous humor after subconjunctival administration,the pmax is 8.030±3.387 mg·L^-1and the tmax is 2 h.The concentration-time data of tetrandrine in aqueous humor was subject to two-compartment open model.The pharmacokinetic parameters were as follows: t_1/2α0.533 h,t_1/2β0.69 h,AUC_0-∞17.762 mg·h·L^-1,K₁₀4.087 h^-1,K₁₂2.787 h^-1,K₂₁ 1.005 h^-1,t_1/2Ka 0.398 h.Conclusion1,The concentration-time processes are found to fit extravascular dose two compartment model after single subconjunctival administration.2,Tetrandrine can penetrate blood-aqueous barrier to enter aqueous humor,its distribution and clearance are fast.3,After single subconjunctival administration of rabbit eyes 5 mg tetrandrine,the pharmacokinetic parameters of tetrandrine in rabbit eyes can provide experiment basis for concrete medication scheme.