[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-eight 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 50 microl drop of 1% voriconazole was administered in group A (non-debrided cornea) and group B (debrided cornea). 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 mm, 5.0 microm) column, Phenomenex C18 (4.0 mm x 3.0 mm, 5.0 microm) analytical steel column and a Waters Empower data workstation. The UV detector was set to 255.0 nm. Methanol-0.04 mol/L ammonium hydroxide (62:38, V/V) was used as mobile phase and the flow rate was 0.8 ml/min. External standard was used in this assay. The pharmacokinetic parameters were calculated with nonlinear least square method by the computer.

Results: Calibration curves were linear over the range 0.1-15.0 mg/L. The concentration at 0.1 mg/L was the lowest quantified limit. 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 dose application, the drug concentration in aqueous humor peaked at 10 min in both group A [ (5.172 +/- 1.012) mg/L] and group B [(6.118 +/- 1.123) mg/L], and the parameters t(1/2 ke) in groups A and B were 6.859 min and 13.176 min, respectively. However, peak drug levels were achieved immediately at 2 min in the cornea [group A: (9.958 +/- 3.481) microg/g and group B: (158.476 +/- 10.462) microg/g]. The parameter t(1/2 beta) in nondebrided cornea was 94.938 min and 46.367 min in debrided 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 dose application. It can be a prominent agent for the treatment of fungal keratitis in the future.