In the lung aerosol cyclosporine provides a regional concentration advantage over intramuscular cyclosporine

Background: Acute rejection remains an almost universal complication among lung transplant recipients. Refractory rejection as well as chronic systemi c immunosuppression is associated with significant morbidity and mortality. Recent studies suggest that aerosol cyclosporine may address these issues by effectively preventing acute cellular rejection while maintaining low sy stemic drug concentrations. This study was designed to evaluate the concent rations of cyclosporine in blood and lung tissue after aerosol and intramus cular administration. Methods: Lewis rats were divided into 4 experimental groups: Groups A (n = 33) and B (n = 30) received aerosol cyclosporine 3 and 5 mg/kg, respectivel y; Groups C (n = 33) and D (n = 30) received systemic cyclosporine 5 and 15 mg/kg, respectively. We used high-performance liquid chromatography to qua ntitate blood and lung tissue cyclosporine levels at timed intervals, We us ed the trapezoidal rule to approximate area under the concentration vs time curve (AUC). Results: Aerosol delivery of cyclosporine resulted in higher and more rapid peak drug levels in lung tissue samples than did systemic delivery, At an equivalent 5 mg/kg dose, the cyclosporine AUC was 3 times higher with aeros ol delivery than with intramuscular delivery in lung tissue (477,965 vs 157 ,706 ng x hour/g, respectively). The lung tissue: blood AUC ratio was highe st in the aerosol groups (27.3:1 and 17.4:1) compared with the intramuscula r groups (8.1:1 and 9.4:1). Conclusion: Local aerosol inhalation delivery of cyclosporine provides a re gional advantage over systemic intramuscular therapy by providing higher pe ak concentrations and greater lung tissue exposure.