Focus | Cyclosporine Inhalation Solution
Cyclosporine Inhalation Solution (CIS) is an inhaled formulation of cyclosporine A, an oral medication that has been widely used for over twenty-five years to prevent rejection in solid organ transplant recipients.
The University of Pittsburgh first put cyclosporine into an aerosol in the late 1980s. Preliminary clinical studies of CIS in lung transplant recipients have been conducted since that time, including a placebo-controlled study that was published as the lead article in the New England Journal of Medicine in January 2006 (Iacono et al 2006). This small, single center, randomized, controlled, phase II study showed that administration of inhaled cyclosporine, initiated soon after transplantation, reduced chronic rejection and improved survival while not increasing the risk of infection. This study led to the multicenter, APT Phase III CYCLIST study.
In both the Phase II and Phase III studies, aerosol doses are administered for approximately thirty minutes, three times per week. The CIS regimen developed by UPMC delivers an average of about 25 mg of cyclosporine to the lungs with each dose, which is significantly higher than the lung dose available with even the most aggressive oral administration regimens. This is important because the preliminary clinical studies suggest that benefit is likely dose-related (Corcoran et al 2004) and high doses of cyclosporine appear to be cleared from the lung more slowly than low doses (Burckart et al 2003). At the same time, pharmacokinetic studies show that CIS does not significantly increase cyclosporine levels in the systemic circulation in those patients concomitantly receiving oral cyclosporine.