Therapeutic monitoring of Cyclosporine (CyA) by using area under the curve (AUC) from abbreviated kinetic profiles is of recent trend in clinical practice due to the potential improvement in transplant and clinical outcome with costs reduction in mind. Several papers describe successful use of the limited sampling strategy to predict AUCs in different transplant populations when treated with Sandimmun or Sandimmun Neoral. However, the same predictive potential is achieved for the latter formulation with lesser effort. The present paper describes the application of the limited sampling strategies to demonstrate the advantages of using CyA incorporated in polymeric nanoparticles (CyA-NP) as compared to two reference Sandimmun formulations which consisted of an emulsion of the oily solution in milk (SIM-EM) and a microemulsion (SIM-Neoral) formerly tried on rats. Two independent data batches were used: group 1 which included 36, 31 and 10 animals receiving SIM-EM, CyA-NP and SIM-Neoral, respectively, and group 2 made of nine and eight rats treated with SIM-EM and CyA-NP. Several limited sampling equations were derived for each formulation from group 1 by stepwise multiple linear regression. Statistical analysis disclosed that CyA concentrations 8 and 32 h after dose administration vouched for 88 and 69% variability in AUC (0-48 h) for CyA-NP and SIM-EM, respectively. When summed up, these two concentrations revealed nearly 97% of AUC (0-48 h) variability. CyA concentrations 8 h post-treatment with SIM-Neoral explained 89% variability in AUC (0-48 h). This value raised to 98% when a second CyA concentration (24 h) was introduced. The equations derived from group 1 were then employed to predict AUCs in group 2. CyA blood levels at 8 h post-treatment confirmed AUC for CyA-NP (r(2)=0.98) to be very precise and unbiased (error=1. 46%, interval -16.2 to 21.33%), while the results for SIM-EM obtained with the CyA concentration at 32 h were r(2)=0.93 plus error=5.71%, interval -44.33 to 105.94%. Similar results were obtained when the study period was reduced to 24 h. The use of these limited sampling models manifested the coincidence between CyA-NP and SIM-Neoral as well as the advantages of both formulations over SIM-EM when it comes to CyA monitoring.