In-vivo Ocular Microdialysis to Monitor Ocularly Applied Cyclosporin in the Anterior Chamber of Rabbits

Abstract

The purpose of this study was to prepare an ophthalmic cyclosporin formulation, reducing its local irritation, and to monitor the concentration of ocularly applied cyclosporin in an anterior chamber using in-vivo ocular microdialysis in rabbits. Oily solutions or emulsions of cyclosporin (0.4 and 2% w/v) were prepared from Sandimmun (10% w/v oral preparation of cyclosporin) by diluting with olive oil or Intralipos (20% w/v injectable lipid emulsion), respectively. These formulations were topically applied to the eye of the rabbit and monitored by ocular microdialysis. The highest concentration of cyclosporin in the anterior chamber was observed within 10 min of ocular application of drug formulations, followed by a gradual decrease until 120 min. The use of emulsion for topical cyclosporin did not influence the pharmacokinetics of cyclosporin in the anterior chamber compared with the application of its oily solution. The therapeutic level of cyclosporin (greater than 80 ng mL−1) in the anterior chamber could be attained by the 0.4% formulation. Local irritation after the instillation of the cyclosporin formulations was examined using the blinking count method. The irritation of the emulsion was significantly diminished compared with the oily solution. The present study suggests that 0.4% (w/v) cyclosporin emulsion is a suitable preparation as the ophthalmic formulation, and that microdialysis is a suitable method for investigation of in-vivo ocular drug pharmacokinetics.