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

Transplantation. 2004 Sep 15;78(5):675-80. doi: 10.1097/01.tp.0000129806.69681.15.

Abstract

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 (OD group, 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 1 year. Five patients per group had reversible acute rejection. There was a not significant trend toward a lower mean serum creatinine in OD than 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 (AUC0-4) and CsA blood levels at 0, 2, and 4 hours after dosing. C0 was significantly lower in OD than in BD (P=0.0011), whereas C2 (P<0.0001) and C4 (P<0.0001) were significantly higher in OD than in BD. In OD, the AUC was higher than in BD (P<0.0001). OD allows 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 rates were observed between OD and BD groups.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Area Under Curve
  • Creatinine / blood
  • Cyclosporine / administration & dosage*
  • Cyclosporine / adverse effects
  • Cyclosporine / pharmacokinetics*
  • Cyclosporine / therapeutic use
  • Drug Administration Schedule
  • Emulsions
  • Female
  • Graft Survival / drug effects
  • Graft Survival / immunology*
  • Histocompatibility Testing
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / pharmacokinetics*
  • Immunosuppressive Agents / therapeutic use
  • Kidney Diseases / classification
  • Kidney Diseases / surgery
  • Kidney Transplantation / immunology
  • Kidney Transplantation / physiology*
  • Male
  • Middle Aged

Substances

  • Emulsions
  • Immunosuppressive Agents
  • Cyclosporine
  • Creatinine