Pharmacokinetics of cyclosporine in monkeys after oral and intramuscular administration: relation to efficacy in kidney allografting

Transpl Int. 2001 Sep;14(5):320-8. doi: 10.1007/s001470100336.


In cynomolgus and rhesus monkeys, the dose-normalized exposure of cyclosporine administered orally as microemulsion preconcentrate (Neoral) was lower than that upon intramuscular administration. For oral administration, mean values ( +/- SD) of Cmax, 24-h area-under-the curve (AUC) and 24-h trough level, all normalized for a 1 mg/kg dose, were 20 +/- 9 ng x kg/mg x ml, 210 +/- 70 ng x h x kg/mg x ml and 2.6 +/- 0.9 ng x kg/mg x ml, respectively. For intramuscular administration, levels were about 5.5-fold, 9-fold and 22-fold higher. Based on pharmacokinetic data, the efficacy of oral cyclosporine treatment (without any other immunosuppressant) was evaluated in life-supporting cynomolgus monkey kidney allotransplantation. Rejection-free kidney allograft survival could be achieved using oral cyclosporine monotherapy with average 24-h trough concentrations above 100 ng/ml during maintenance treatment. Typically, daily oral doses of 100 mg/kg-150 mg/kg during the first two weeks post-transplantation, followed by daily 30 mg/kg-100 mg/kg dose levels during subsequent maintenance can result in long-term allograft survival, with 24-h average trough levels in individual animals during maintenance between 110 ng/ml and 700 ng/ml.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Cyclosporine / administration & dosage
  • Cyclosporine / pharmacokinetics*
  • Female
  • Graft Rejection / prevention & control
  • Graft Survival / drug effects
  • Graft Survival / immunology*
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / pharmacokinetics*
  • Injections, Intramuscular
  • Kidney Transplantation / immunology*
  • Macaca fascicularis
  • Macaca mulatta
  • Male
  • Metabolic Clearance Rate


  • Immunosuppressive Agents
  • Cyclosporine