Article
Microdialysis as a promising new method to assess the ocular pharmacokinetics of topical eye drops in a rabbit animal model
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Authors
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Gerhard Garhöfer
- Univ. Klinik für Klinische Pharmakologie, Wien, Austria
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Robert Klaus
- Zentrum für Medizinische Physik, Wien, Austria
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Walter Jäger
- Department für Klinische Pharmazie und Diagnostik, Wien, Austria
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Markus Zeitlinger
- Univ. Klinik für Klinische Pharmakologie, Wien, Austria
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Leopold Schmetterer
- Univ. Klinik für Klinische Pharmakologie, Wien, Austria
| Published: | September 24, 2015 |
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Outline
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Background: Although topical drug delivery is the most widely used drug administration route for the treatment of ocular diseases, studies regarding the in-vivo pharmacokinetics of topically applied drugs are sparse. The current study was designed to investigate whether microdialysis is a suitable method to gain a robust in-vivo pharmacokinetic profile of topically applied drugs. For this purpose, in-vivo microdialysis of the anterior chamber and the vitreous was performed in a rabbit model to assess the pharmacokinetics of topically applied ciprofloxacin eye drops.
Methods: 8 Female New Zealand White rabbits (Charles River, Germany) weighing 2.3 - 4.1 kg were included in the experiments. Under general anesthesia, a linear microdialysis probe was implanted in the anterior chamber and a concentric microdialysis probe in the posterior segment of the same eye. After a run-in period of 2 hours, one single drop (30µl) of ciprofloxacin eye drops (0.09mg in 30μl) was administered on the ocular surface. Microdialysis samples of the anterior chamber and the vitreous were collected every 30 min for 6h. Finally, relative recovery was assessed by retro-dialysis to calculate absolute concentration values. Samples were analyzed using HPCL.
Results: In the anterior chamber, the maximum free drug concentration (Cmax) amounted to 0.373±0.281 µg/ml and was reached (Tmax) after 116±36 minutes. Calculated AUC (0-n) for ciprofloxacin in the anterior chamber was 78.8±47.1 mg min/ml. For the vitreous, Cmax was 0.002±0.003 µg/ml and maximum drug concentration was reached 106±60 min after topical administration. AUC (0-n) for ciprofloxacin in the vitreous was 0.268±0.370 mg min/ml.
Conclusion: Microdialysis is a suitable method to assess in-vivo pharmacokinetic profiles in the anterior chamber and in the vitreous. In the anterior chamber maximum drug concentration was reached approximately 2 hours after single drug administration. Although the drug concentration in the vitreous was considerably lower, time course of drug concentration was comparable.
