Ocular penetration and pharmacokinetics of topical voriconazole in rabbit eyes

Objective To investigate the penetration of topical 1%voriconazole into the cornea and aqueous humor in New Zealand white rabbits.Methods It was a experimental study.Forty-eisht healthy rabbits were randomly divided into groups A(21 cases),B(21 cases)and C(6 cases).Blank samples from group C were used to determine the essential parameters for the validation of analytical procedures.A single 50μl drop of 1%voriconazole Was administered in group A(non-debrided cornea)and group B (debrided comea).The aqueous humor and the cornea were obtained at 2,5,10,15,30,60 and 90 min after application.All samples were analyzed by high-performance liquid chromatography(HPLC).The HPLC system consisted of Waters 1525 pump,Phenomenex Luna C18(250.0 mm x 4.6 inin,5.0μm) column,Phenomenex C18(4.0 mm×3.0 mm,5.0μm)analytical steel column and a Waters Empower data workstation.The UV detector Was set to 255.0nm.Methanol-0.04 moL/L ammonium hydroxide(62:38,V/V) was used as mobile phase and the flowrate Was 0.8 ml/min.External standard Was used in this assay.The pharmaeokinetie parameters were calculated with nonlinear least square method by山e compute- Resuits Calibration curves were linear over the range 0.1～15.0 ms/L The concentration at 0.1 m/L was the lowest quantified limiL The recovery of voriconazole from aqueous humor samples ranged from 91.06%tO 94.80%.and ranged from 79.84% to 83.20%in the cornea samples.After single doseapplication,the drug concentration in aqueous humor peaked at 10 min in both group A[(5.172±1.012)me/L]and group B[(6.118 +-1.123)mg/L],and the parameters tl/2 kg in groups A and B were6.859 min and 13.176 min,respectively.However,peak drug levels were achieved immediatelv at 2 min in the cornea [group A:(9.958 4-3.481)μg/g and group B:(158.476 -+10.462)μg/g].The parameter t1/2B in nondebfided cornea was 94.938 min and 46.367 min in debfided corneas.Conclusions Topical voriconazole exhibits excellent penetration into the cornea,and effective high drug levels are achieved in both the cornea and aqueous humor after single d08e application.It can be a prominent agent for the treatment of funsal keratitis in the future. Key words: Triazoles; Pyfimidines; Ophthalmic solutions;  Chromatography high pressure liquid; Pharmacokineties