家兔静脉注射左氧氟沙星后的眼内组织分布及其药动学研究

Study on the Distribution and Pharmacokinetics of Levofloxacin in Ocular Tissue of Rabbits after Intravenous Administration

目的:研究家兔静脉注射左氧氟沙星后的眼内组织分布及药动学。方法:27只家兔单剂量静脉注射左氧氟沙星(24mg/kg)后0.125、0.5、1.0、2.0、3.0、4.0、6.0、8.0、12.0h处死并取眼球各组织制备成匀浆,以高效液相色谱法测定眼内各组织中的药物浓度,3p97软件计算药动学参数。结果:给药后房水、角膜、虹膜-睫状体、玻璃体和晶体组织中药物cmax分别为(4.93±0.83)μg/ml,(6.12±0.71)、(6.02±0.55)、(1.98±0.28)、(1.38±0.12)μg/g;tmax分别为(0.50±0.00)、(0.83±0.26)、(0.71±0.71)、(0.52±0.28)、(0.67±0.26)h;t1/2β分别为(2.53±0.65)、(3.20±0.32)、(3.34±0.46)、(2.74±0.78),(2.49±0.45)h;AUC0-12h分别为(11.46±1.42)μg·h/ml,(28.01±1.59)、(26.01±2.34)、(8.16±0.85)、(5.23±0.89)μg·h/g。除房水为二室模型外,其余均呈一室模型分布。结论:家兔单剂量静脉注射左氧氟沙星后在眼内各组织中分布浓度较高,达峰时间较快,但保留时间相对较短。

OBJECTIVE：To study the distribution and pharmacokinetics of levofloxacin in ocular tissue of rabbits after intravenous administration.METHODS：27 rabbits were given intravenous administration of levofloxacin 24 mg/kg and scarified 0.125,0.5,1.0,2.0,3.0,4.0,6.0,8.0 and 12.0 h after administration.The various samples of ocular tissues were collected to prepare homogenate.The concentrations of levofloxacin were measured by HPLC,and pharmacokinetic parameters were calculated using 3p97 software.RESULTS：Main pharmacokinetic parameters of levofloxacin in aqueous humor,cornea,iris-ciliary body,vitreous body and lens were as follows：cmax were（4.93±0.83）μg/ml,（6.12±0.71）,（6.02±0.55）,（1.98±0.28）and（1.38±0.12）μg/g;tmax were （0.50±0.00）,（0.83±0.26）,（0.71±0.71）,（0.52±0.28）and（0.67±0.26）h,respectively;t1/2 β were（2.53±0.65）,（3.20±0.32）,（3.34±0.46）,（2.74±0.78）and（2.49±0.45）h;AUC0-12 h were（11.46±1.42）μg·h/ml,（28.01±1.59）,（26.01± 2.34）,（8.16±0.85）and（5.23±0.89）μg·h/g,respectively.The pharmacokinetics of levofloxacin in all tissues conformed with one-compartment open model except in aqueous humor.CONCLUSION：Levofloxacin is in a higher level in various ocular tissues of rabbits after intravenous administration of single dose,reaches peak concentration rapidly and maintains for short time in tissues.