Comparison of the Ocular Penetration and Pharmacokinetics Between Natamycin and Voriconazole After Topical Instillation in Rabbits.

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.