Cyclosporine (CsA) is an effective immunosuppressant drug. Recently a new oral formulation, Sandimune Neoral (SIM-NOF) has been developed to overcome the problems of poor bioavailability, unpredictable blood levels and variable gastro-intestinal absorption seen with the use of traditional Cyclosporine, Sandimune (SIM). We conducted a prospective, open label crossover tolerability, efficacy and safety of SIM-NOF and (2) to compare SIM-NOF with SIM for their bioavailability, absorption pattern and consistence of 12-hour trough levels. Fourteen renal transplant recipients, with stable renal function (serum creatinine stable for more than six immediate previous months) and SIM dosages, were randomly selected for the study. Their age mean +/- SD 38.2+/- 11.1 years, ad had completed 3.8+/- 2.2 years after transplantation. All patients were on triple drug immunosuppression with prednisone, azathioprine and SIM. The study consisted of an initial 12-week period, where SIM was used and cyclosporine 12-hour trough levels were monitored t least every four weeks. This was followed by a run-in period of two weeks, where a 12-hour cyclosporine profiling was done while patients were on SIM. This was followed by a 12-week period, Where SIM-NOF replaced SIM on a 1:1 dose conversion ratio. During this latter period, 12-hour trough levels (at 1,2,3,8 and 12 weeks) were measured. The doses of the SIM-NOF were adjusted to maintain blood cyclosporine trough levels at 50-180 mug/ml. On cyclosporine profiling, SIN-NOF showed a predictable and constant absorption profile peaking at two hours in all instances with steady declining levels through the following ten hours. With SIM the levels were unpredictable and erratic. The Tmax for SIM-NOF was 2.0+/- 0 hours and for SIM 3.7+/- 1.7 hours (p< 0.0001). The Cmax for SIM- NOF was 2149 and for SIM 1942 (p=0.008). The 12-hour trough studies for SIM-NOF is a superior preparation to SIM in clinical practice. No specific adverse effects were observed.
