Overview of the clinical experience with Neoral in transplantation

The microemulsion preparation of cyclosporine, Neoral, was introduced to improve the limited and sometimes unpredictable absorption of cyclosporine from the gut. Preclinical studies proved a superior bioavailability measured by the AUC and a definitively better predictability of the pharmacokinetic properties. Large-scale randomized and open-labeled studies have been carried out to prove and establish the safety, tolerability, and equal or superior efficacy of NEO if compared with SIM. There is broad evidence that NEO is safe and well tolerated in de novo and stable renal allografts. There are some arguments that NEO has favorable properties in poor absorbers, in patients in need for high dosage per kg body weight. Benefits for some populations such as children, African Americans, and diabetics have been detected. In combined kidney-pancreas transplantation a significant improvement of absorption has been proven. NEO has also been investigated in nonrenal transplants such as heart, lung, and liver transplantation. There are proven dose reduction in heart transplants; significant better absorption in lung transplants, in particular in patients with cystic fibrosis; and no further or even a diminished need for intravenously given CsA in liver transplantation. Studies are now reported for the use of NEO in differing indications of autoimmune disease. No characteristic profile of adverse events has been recognized, nor has an increase of nephrotoxicity if carefully monitoring in the first weeks after conversion was provided.