Purpose: To investigate the ocular penetration of natamycin (NAT) and voriconazole (VRC) after topical instillation in New Zealand white rabbits using simplified liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high-performance liquid chromatography.
Methods: Seventy-eight healthy rabbits were randomly divided into 3 groups. In the first 2 groups, 72 rabbits were used for single-dose testing (36 for NAT, 36 for VRC), in which 50 μL of 5.0% NAT or 1.0% VRC was instilled into the rabbits' left eyes. In the 3rd group, 6 rabbits were used for repeated-dose testing in which 50 μL of 5.0% NAT was instilled into their left eyes 12 times (once per hour) during the daytime. These animals were sacrificed immediately to collect their aqueous humors and corneas.
Results: After a single topical instillation, the highest concentrations in the cornea and aqueous humor for VRC were 34.1 μg/g and 14.7 μg/mL, respectively. The permeability ratios of aqueous/cornea were from 0.1 to 1.26. The highest concentrations in cornea and aqueous humor for NAT were 299.3 ng/g and 27.1 ng/mL, respectively. The permeability ratios of aqueous/cornea were from 0.02 to 0.23. In the repeated-dose group, the NAT concentrations in the cornea and aqueous humor were 10,569 ng/g and 54.4 ng/mL, respectively. The permeability ratio was as low as 0.0051.
Conclusion: The better corneal penetration of VRC suggests that it is more suitable for deep corneal fungal infections than NAT via topical ocular administration.
Keywords: LC-MS/MS; natamycin; penetration; pharmacokinetics; voriconazole.