Study on pharmacokinetic of vancomycin in normal and endophthalmitis eyes in rabbit / 中华实验眼科杂志

ABSTRACT

Background Vancomycin has been increasingly recommended for the management of endophthalmitis,but few research report has been published about the pharmacokinetics of intravitreal vancomycin up to now.It is necessary to have an exact method to measure the concentration of vancomyein in animal eyes after intravitreal injection.Objective This study was to observe and compare the phamacokinetical process of vancomycin in serum,vitreous and aqueous humor between normal and infected rabbit eyes.Methods Seventy-two healthy adult rabbits were randomly divided into normal group and infected group and 36 rabbits for each.The animal models of endophthalmitis were established by intravitreal inoculation of 2000 CFU/ml staphylococcus aureus in the right eyes of rabbits in the infected group.Once endophthalmitis developed,0.1 ml vancomycin ( 10 g/L) solution was injected into the vitreous of every rabbit.The peripheral blood,vitreous and aqueous humor samples were respectively collected in 4 rabbits for each group at 0.5,2,4,6,12,24,48,72 and 84 hours after injection for detection of vancomycin concentration by high performance liquid chromatography(HPLC-UV).3p97 software was used to create fit parameters of pharmacokinetics.This experiment followed the Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission (Version 1988).Results The accuracy of HPLC fitted the detecting request of biological specimen.The concentration-time data of vancomycin in normal rabbit aqueous humor and vitreous was subject to two-compartment model.The pharmacokinetic parameters were separately as followingCmax was 50.16 mg/L and 751.42 mg/L,t1/2was 51.04 hours and 53.21 hours.The concentration-time data of vancomycin in infected rabbit aqueous humor and vitreous was subject to one-compartment model.The pharmacokinetic parameters were separately as followingCmaxwas 24.94 mg/L and 687.66 mg/L,t1/2was 11.42 hours and 12.91 hours.The concentration of vancomycin in serum was much lower and almost undectable.The concentration of vancomycin in vitreous was gradually reduced as the prolong of time after injection in both normal group and infected group,but a obvious decline after increased level was scen in aqueous humor.Compared with normal group,the concentrations of vancomycin in both vitreous and aqueous humor were reduced at various time points(P＜0.05,P＜0.01 ).Conclusions HPLC is simple,highly sensitive and specific for the pharmacokinetic analysis of vancomycon.These results indicate that pharmacokinetic parameters of vancomycin alter in pathological condition,which is helpful for us to establish the better treatment guidelines for endophthalmitis.