Is cyclosporine in renal-transplant recipients more effective when given twice a day than in a single daily dose?

Background. It is still unknown whether it is better to administer cyclosporine (CsA) once or twice a day to renal-transplant patients. Methods. Fifty-four patients were randomized to receive CsA once a day ( ODgroup, 28 patients) or twice a day (BD group, 26 patients). Clinical parameters and pharmacokinetic studies were regularly monitored over the first year. Results. Two patients lost their grafts because of renal vascular thrombosis. A patient in the BD group died. The other 51 patients were alive with graft functioning after a minimum follow-up of I year. Five patients per group had reversible acute rejection. There was a not significant trend toward a lower mean serum creatinine in ODthan in BD (1.38±0.38 and 1.7±0.80 mg/dL at 1 year posttransplant, respectively). In 47 patients, 319 pharmacokinetic studies were performed. We measured the area under the concentration-time curve during the first 4 hours (AUC 0-4 ) and CsA blood levels at 0,2, and 4 hours after dosing. CO was significantly lower in ODthan in BD (P=0.0011), whereas C2 (P<0.0001) and C4 (P<0.0001) were significantly higher in ODthan in BD. In OD, the AUC was higher than in BD (P<0.0001). ODallows us to reach high levels of C2 and AUC for several hours after dosing, whereas BD showed persistently high levels throughout the whole day. Conclusion. No difference in survival and rejection rateswere observed between ODand BD groups.