A pharmacokinetic study of vancomycin injected into the vitreous of rabbit eyes with endophthalmitis in different pathological conditions

Abstract

Objective To observe the concentration of vancomycin and the changes of pharmacokinetic parameters in rabbit vitreous with endophthalmitis in different pathological conditions.Methods Eighty-one adult healthy rabbits were randomly divided into endophthalmitis with lens group (group A),aphakic endophthalmitis group (group B),aphakic endophthalmitis and vitrectomy group (group C),27 rabbits in each group.The right eyes of all rabbits received intravitreal injection of 1 ml (10 mg/ml) vancomycin.Three rabbits from each group were sacrificed at 0.5,2.0,4.0,6.0,12.0,24.0,48.0,72.0,84.0 hours after the injection.The eyes were harvested to collect the vitreous.The vitreous concentrations of vancomycin in all the groups were detected by high performance liquid chromatography (HPLC-UV).The pharmacokinetic parameters including the area under the curve (AUC) of the concentration-time graph,clearance rate (CL),half-life period (t1/2) and peak concentration (Cmax) were calculated by 3p 97 pharmacokinetic software.Results The concentrations of vancomycin in the group A were always higher than the therapeutic drug levels after injection.In the group B and C,the concentrations of vancomycin remained significantly high at 0.5,2.0,4.0,6.0 and 12.0 hours after injection,decreased quickly at 24 and 48 hours after injection,below the minimal inhibitory concentrations at 72 hours after injection.The differences were statistically significant among group A,B and C (t =4.968,5.232; P＜0.05),but not statistically significant between group B and C (t=1.279,P＞0.05).The AUC were 15 790.61,7643.94,7443.44 μg/(ml · h),CL were 0.063,0.131,0.134 ml/h,t1/2 were 13.49,7.15,6.93 hours and Cmax were 711.56,648.45,667.74 μg/ml in the group A,B and C,respectively.In the group A,the CL was lower (t=2.963,3.097 ; P＜0.05 ) and t1/2 was longer (t=3.315,3.481 ; P＜0.01 ) than those in the group B and C,but there was no significant difference on Cmax (t =1.687,1.214;P＞0.05).Conclusion The pharmacokinetic parameters of vancomycin in rabbit vitreous with endophthalmitis varied between different pathological conditions. Key words: Endophthalmitis/ drug therapy; Vancomycin/administration & dosage; Pharmacokinetics; Disease models, animal