结膜下注射维拉帕米后在组织的分布及药代动力学特点

Comparative studies on the distribution and pharmacokinetics of Verapamil following subconjunctival administration in an experimental model of PVR

目的 研究结膜下给药兔眼玻璃体、房水及血浆中维拉帕米的分布及药代动力学特点。方法 制备外伤性增生性玻璃体视网膜病变 (proliferative vitreuretinopathy,PVR)动物模型 ,结膜下注射 2 .5 g· L- 1 维拉帕米 0 .5 m L ,按时抽取玻璃体、房水及血液样品。样品经提取、浓缩处理后 ,采用美国 HP10 5 0 HPL C系统测定样品中维拉帕米的浓度 ,计算其药代动力学参数。结果 玻璃体的药代动力学参数 :t1 / 2 (Ke) =(6.42± 2 .2 4) h,T(peak) =(1.96± 0 .64 ) h,Cmax=(17.61± 4.60 ) mg· L- 1 ,AUC=(2 0 0 .2 0± 46.5 0 ) mg·L- 1 · h- 1 。房水的药代动力学参数 :t1 / 2 (Ke) =(2 .73± 1.0 2 ) h,T(peak) =(0 .74± 0 .2 2 ) h,Cmax=(2 1.5 3± 5 .2 0 ) mg· L- 1 ,AU C=(99.3 2± 3 2 .40 ) mg· L- 1· h- 1。血浆的药代动力学参数 :t1 / 2 (Ke) =(2 .3 4± 1.2 0 ) h,T(peak) =(3 .0 5± 1.0 2 ) h,Cmax=(0 .2 6± 0 .10 ) m g·L- 1 ,AU C=(1.95± 0 .84) mg· L- 1 · h- 1 。结论 结膜下注射维拉帕米兔眼玻璃体、房水及血浆中的药代动力学参数存在明显差异 (P<0 .0 5或 0 .0 1) ,维拉帕米在玻璃体及房水中能达到有效治疗浓度 ,为结膜下注射维拉帕米防治

Objective To study the distribution and pharmacokinetic parameters of Verapamil following subconjunctival administration.Methods An experimental model of traumatic proliferative vitreoretinopathy(PVR) was produced in pigment rabbits, then subconjunctival Verapamil injection was carried out. The concentrations of Verapamil in vitreous, aqueous and plasma at various time were determined by a reversed phase HPLC, and the pharmacokinetic parameters were analyzed by 3P87. Results The pharmacokinetic parameters were as follows: Vitreous: t 1/2 (Ke) =(6.42±2.24)h, T(peak)=1 96±0.64)h, C max =(17.61±4.60)mg·L -1 , AUC=(200.20±46.50)mg·L -1 ·h -1 ; Aqueous: t 1/2 (Ke)=(2.73±1.02)h, T(peak)=(0.74±0.22)h, C max =(21.53±5.20)mg·L -1 , AUC=(99.32±32.40)mg·L -1 ·h -1 ;Plasma:t 1/2 (Ke)=(2.34±1.20)h; T(peak)=(3.05±1.02)h, C max =(0.26±0.10)mg·L -1 ; AUC=(1.95±0.84)mg·L -1 ·h -1 . Conclusion The pharmacokinetic parameters of Verapamil in vitreous, aqueous and plasma following subconjunctival administration are signifcantly different( P <0.05 or 0.01). The results provide the basis of subconjunctival Verapamil for the treatment of PVR and other eye diseases.