Related Experiment Video
Updated: Jul 5, 2026
Use of Rabbit Eyes in Pharmacokinetic Studies of Intraocular Drugs
Published on: July 23, 2016
Aqueous humor concentration of voriconazole after topical administration in rabbits
Christian K Vorwerk1, F Streit, L Binder
1Department of Ophthalmology, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120, Magdeburg, Germany.
Objectives:
Voriconazol is a triazole antifungal drug with in vitro fungicidal activity against all Candida spp., Fusarium spp. and Aspergillus spp. which are frequent causes of fungal keratitis depending on geographic location. We investigated the penetration of voriconazole through the cornea into the aqueous humor (AH) after topical administration.
Methods:
A 1% voriconazole solution was applied onto each rabbit's cornea. Topical drug application was processed at different time intervals: single drug application with AH sampling after 30 min, 1 h, 2 h, 3 h and 6 h. In addition, we evaluated AH samples after repeated topical application of voriconazole every 30 min after 1, 2, 4 and 6 h. Furthermore, after repeated drug application every hour, we analyzed voriconazole concentration after 2, 3, 4 and 6 h. All samples were analyzed by high-performance liquid chromatography (HPLC)-UV.
Results:
A single application showed a maximum peak in AH of 3.58 microg/ml (N = 9) after 30 min. Within 3 h the concentration decreased to 0.04 microg/ml (N = 11). Application of voriconazole every half an hour revealed a peak value of 6.73 microg/ml (N = 10) after 2 h; after 4 h the value decreased to 6.19 microg/ml (N = 10) and was constant after 6 h (6.12 microg/ml, N = 6). When administrated every hour, only lower AH concentrations of voriconazole were reached with a maximum level of 2,06 microg/ml (N = 8) after four hours.
Conclusion:
In AH, therapeutic drug levels that cover the minimum inhibitory concentrations (MIC) of most fungi can be reached. To achieve a sustained high level of voriconazole as an effective antifungal therapy for corneal keratitis, voriconazole should be topically administered every 30 min.
Insights
Topical voriconazole effectively reaches therapeutic levels in the aqueous humor for fungal keratitis treatment. Frequent administration every 30 minutes ensures sustained drug concentrations for optimal antifungal therapy.
Area of Science:
- Ophthalmology
- Pharmacology
- Mycology
Background:
- Fungal keratitis is a serious eye infection caused by various fungi.
- Voriconazole is a potent triazole antifungal with in vitro activity against common keratitis pathogens.
- Understanding voriconazole penetration into the aqueous humor is crucial for effective treatment.
Purpose of the Study:
- To investigate the penetration of voriconazole into the aqueous humor (AH) after topical ocular administration.
- To determine optimal dosing intervals for achieving therapeutic voriconazole concentrations in the AH.
- To evaluate the potential of topical voriconazole for treating fungal keratitis.
Main Methods:
- A 1% voriconazole solution was applied topically to rabbit corneas.
- Aqueous humor samples were collected at various time points after single and repeated applications.
- Voriconazole concentrations were quantified using high-performance liquid chromatography (HPLC)-UV.
Main Results:
- A single topical application resulted in a peak AH concentration of 3.58 microg/ml at 30 minutes.
- Repeated administration every 30 minutes achieved a sustained peak concentration of 6.73 microg/ml at 2 hours.
- Less frequent (hourly) administration yielded lower AH voriconazole levels.
Conclusions:
- Topical voriconazole can achieve therapeutic concentrations in the aqueous humor.
- Frequent topical administration (every 30 minutes) is recommended for sustained high drug levels.
- This dosing strategy supports voriconazole's use as an effective treatment for fungal keratitis.
