Abbreviated kinetic profiles in area-under-the-curve monitoring of cyclosporine therapy Technical Note

Abbreviated kinetic profiles in area-under-the-curve monitoring of cyclosporine therapy. Technical Note.BackgroundThe new microemulsion formulation of cyclosporine (CsA-ME) displays more consistent pharmacokinetic properties than the original formulation and may allow successful implementation of an abbreviated area-under-the-curve (AUC) strategy.MethodsHere we compared two limited sampling strategies in order to define the one that best predicts AUC after CsA-ME in 51 renal transplant recipients with stable renal function. Pharmacokinetics were based on analysis of blood samples collected over 12hours after drug administration by high-performance liquid chromatography (HPLC). Predicted AUC was estimated by using a three-point (0, 1 and 3hr) or a two-point (2 and 6hr or 0 and 2hr) sampling strategy.ResultsA simplified strategy with three time points of blood collection at 0, 1, and 3hours after CsA-ME allowed adequate and accurate prediction of the daily exposure to CsA. AUC prediction with two-point sampling at 2 and 6hours was less good with a very large error in prediction (only 59% of the estimated AUC were within the accepted range). This limitation was even more evident when the 0 and 2hour time points were examined, in which only 51% of AUC estimates were included in the accepted range of variation (-10 to 10%).ConclusionsA limited strategy of three-point sampling taken early after dosing allows an excellent and perfectly reliable prediction of the actual AUC