FIRST PHARMACOKINETIC STUDY WITH SDZ RAD IN STABLE LUNG TRANSPLANT RECIPIENTS

Abstract

743 Background: SDZ RAD (RAD), a new immunosuppressant related to sirolimus, inhibits growth factor-driven proliferation of T cells and fibroblasts. The latter effect has shown to be of relevance in preclinical models of allograft obliterative airway disease. Objectives: To determine the pharmacokinetics (PK) of RAD at two different single oral doses in stable lung transplant recipients with and without cystic fibrosis (CF). Methods: Two single oral doses of 0.035 and 0.1 mg/kg of RAD up to 75 kg were investigated in a single center, randomized, double-blind, crossover design with a washout of 15 days after the first dose. Patients with(n=3) and without (n=11) CF were receiving Neoral® twice daily (total daily dose 225-800 mg) in combination with ≤ 20 mg/day of prednisone. RAD and CsA in whole blood were measured on Days 1 and 16 and the latter also at baseline (without RAD). Results: Patients (6 males/8 females) had body weights of 59±15 kg (CF) and 79±15 kg (NON-CF). Cmax and AUC differed 3-fold between the high and low dose groups in NON-CF vs about 2-fold in CF patients. RAD absorption was delayed and systemic exposure reduced in the CF compared to the NON-CF cohort. Both single oral doses of RAD did not affect the PK of CsA in NON-CF patients. RAD was well tolerated in this study.TableConclusion: The preliminary single dose PK of SDZ RAD in stable lung transplant recipients without CF were similar to that reported in a previous single dose study in stable kidney transplant recipients. Further investigation of RAD PK especially in CF patients is warranted.