雷公藤多甙滴眼液眼内药代动力学的实验研究

Studies on pharmacokinetics of triptriolide ophthalmic solution in rabbit eye

目的 首次研制出雷公藤多甙（TⅡ）滴眼液,并用高效液相色谱仪法对该滴眼液的药代动力学参数进行研究。方法 将0.03％TⅡ滴眼液50μl滴入兔眼下睑结膜囊内,在4h中定时采取房水做为测试样本,经处理后,用高效液相色谱仪测定样本中的雷公藤内酯醇质量浓度。结果TⅡ滴眼液在新西兰白兔眼内为一室模型,主要药代动力学参数为:A=2.703 μg/Ml;Ke=2.047h-1;Ka=2.708h-1;Lagtime=0.456h;t1/2（ka）=0.256h;t1/2（ke）=0.339h;T（max）=0.880h;C（max）=0.278μg/ml;AUC=0.323μg/（h·ml）。其拟合的动力学方程为C（t）=178.123×Dose× （e-2.047×（t-0.456）-e-2.708×（t-0.456））。结论TⅡ滴眼液眼内有效峰浓度出现在点药后0.88h,4h基本被代谢消除。

ve To observe the pharmacokinetic experiment of the triptriolide ( TⅡ) ophthalmic solution in rabbit eyes by high performance liquid chromatography( HPLC). Methods Aqueous humor levels of triptolide were determined by intervals within 4 h by HPLC following 50 μ10. 03% TⅡ eye drops application in rabbit conjunctive. Results The aqueous humor concentration-time experiment was shown to be subjected to one-compartment model. The parameters of pharmacokinetic of the Triptriolide in rabbit aqueous humor average equation were A = 2. 703 μg/ml; Ke = 2. 047 h -1; Ka = 2. 708 h -1 ; Lagtime = 0. 456 h; t1/2 ( ka )= 0. 256 h;t1/2(ke) =0.339 h;T(max) =0.880 h;C(max) =0.278 μg/ml;AUC =0. 323 μg ?h ?ml-1. Conclusion The peak concentration of the TⅡ ophthalmic solution is in 0. 88 h applied, and vanished in 4 h.