Pharmacokinetics Of Levofloxacin And Clopidogrel On Carbonated Eye Drops In Rabbit Eyes

In this paper, the compound Loteprednol etabonate Levofloxacin Eye Drops (LEL)、Levofloxacin Eye Drops (LVFX) or Loteprednol etabonate Eye Drops (LE) applied locally in the eyes of rabbits for 4 weeks respectively. The concentration of the Levofloxacin or Loteprednol etabonate in the rabbit eye tissue samples such as cornea, aqueous humor, iris-ciliary body, lens, vitreous body were measured by high performance liquid chromatography (HPLC). The pharmacokinetics parameters were compared between LEL group、LVFX group and LE group to investigate the rationality of the compound LEL.The results shows the pharmacokinetic parameters of LEL group are:Tmax:cornea:0.25 h, aqueous humor:1.0 h, iris-ciliary body:0.5 h, lens:0.5 h, vitreous body:0.25 h; Cmax: cornea:25.368μg/g, aqueous humor:2.558μg/ml, iris-ciliary body:1.426μg/g, lens:0.060μg/g, vitreous body:0.063μg/ml; T1/2: cornea:1.69 h, aqueous humor:1.13 h, iris-ciliary body:3.17 h, lens:2.24 h, vitreous body:1.44 h.The pharmacokinetic parameters of LVFX group are:Tmax:cornea:0.25 h, aqueous humor:1.0 h, iris-ciliary body:0.25 h, lens:0.5 h, vitreous body:0.25 h; Cmax:cornea: 23.045μg/g, aqueous humor:1.849μg/ml, iris-ciliary body:1.423μg/g, lens:0.055μg/g, vitreous body:0.065μg/ml; T1/2:cornea:3.02 h, aqueous humor:1.26 h, iris-ciliary body: 2.80h, lens:6.85 h, vitreous body:2.23 h.The ratios of AUC0-t of Levofloxacin after eye drop LEL and LVFX are:cornea:1.20, aqueous humor:1.02, iris-ciliary body:0.90, lens:1.15, vitreous body:1.00. Compare the ratios of AUC0-t, the LEL group were no difference with LVFX group.Only in the cornea and aqueous humor detected Loteprednol etabonate or its metabolites PJ91, and other eye tissues were not detected or only detected part of the prototype drug or its metabolites PJ91, also, another major metabolite of Loteprednol etabonate PJ90 were not measured in most eye tissues. Compare the concentrations changes between LEL group and LE group, the concentration of Loteprednol etabonate in the rabbit cornea was no significant difference, and there were no significant differences in the rabbit cornea and aqueous humor about the metabolite of Loteprednol etabonate PJ91.After that the composition of compound proved there is no influence about the two drugs in the rabbit eye tissue distribution.