Cyclosporine Plexis formulation release data

The goal of this research is to reduce toxicity and graft rejection due to dosing problems with cyclosporine by developing sustained release subcutaneous injectable formulations. Even frequent drug monitoring cannot eradicate rejection due to sub-therapeutic troughs or toxicity because of higher than necessary peak levels. In addition, non-adherence with the daily oral dosing regimen is a major cause of graft failure, especially in adolescent patients. Pharmacokinetic modeling suggests that periodic subcutaneous dosing can reduce or eliminate many of these problems.

The first graph shows the in vitro release of cyclosporine for greater than 400 hrs.

Suspensions of cyclosporine (dose 30 mg/kg) were used for a pharmacokinetic and safety study. Studies using conventional intravenous dosing have demonstrated an elimination half life of 10.7 hours for cyclosporine in the rat. In contrast, the present work demonstrates sustained release for greater than 28 days.