In‐vivo microdialysis as a new technique to assess ocular pharmacokinetics of topically applied drugs in a rabbit model

Abstract

PurposeAlthough topical drug delivery is the most widely used ocular drug administration route, the in‐vivo pharmacokinetic profile of topically applied drugs is only inadequately described. This is mainly caused by the fact that in the eye the assessment of in‐vivo pharmacokinetics is difficult and technically demanding. Here, we propose a new technique for the in‐vivo assessment of pharmacokinetic parameters of topically applied drugs using in‐vivo microdialysis in a rabbit model.Methods8 Female New Zealand White rabbits were included in the experiments. A linear microdialysis probe (30 kDa molecular weight cut off [MWCO]) was implanted in the anterior chamber, a concentric probe (20 kDa MWCO) in the posterior segment of the same eye. After a run‐in period to obtain stabile conditions, a single drop of ciprofloxacin eye drops was administered on the cornea. Microdialysis samples were collected every 30 min for 6 h. Probes were analyzed using HPCL.ResultsIn the anterior chamber, the maximum total drug concentration was reached after 116 ± 36 minutes (Tmax) and amounted to 0.373 ± 0.281 μg/ml (Cmax). AUC (0‐n) for ciprofloxacin in the anterior chamber was 78.8 ± 47 μg min/ml. In the vitreous, drug concentration was considerably lower. A Cmax of 0.02 ± 0.03 μg/ml was reached after 106 ± 60 min. AUC (0‐n) for ciprofloxacin in the vitreous was 0.286 ± 370 μg min/ml.ConclusionsHere, we present in‐vivo microdialysis as a new method for the in‐vivo assessment of pharmacokinetic profiles. Maximum drug concentration in the anterior chamber 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. In summary, our data show that microdialysis is an excellent method to assess in‐vivo pharmacokinetics with a high temporal resolution.