F Gaspari1, N Perico, O Signorini, R Caruso, G Remuzzi. 1. Department of Transplant Immunology and Innovative Antirejection Therapies, Ospedali Riuniti Bergamo, Mario Negri Institute for Pharmacological Research, Italy. gaspari@irfmn.mnegri.it
Abstract
BACKGROUND: The 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. METHODS: Here 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 12 hours after drug administration by high-performance liquid chromatography (HPLC). Predicted AUC was estimated by using a three-point (0, 1 and 3 hr) or a two-point (2 and 6 hr or 0 and 2 hr) sampling strategy. RESULTS: A simplified strategy with three time points of blood collection at 0, 1, and 3 hours after CsA-ME allowed adequate and accurate prediction of the daily exposure to CsA. AUC prediction with two-point sampling at 2 and 6 hours 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 2 hour time points were examined, in which only 51% of AUC estimates were included in the accepted range of variation (-10 to 10%). CONCLUSIONS: A limited strategy of three-point sampling taken early after dosing allows an excellent and perfectly reliable prediction of the actual AUC.
BACKGROUND: The 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. METHODS: Here 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 12 hours after drug administration by high-performance liquid chromatography (HPLC). Predicted AUC was estimated by using a three-point (0, 1 and 3 hr) or a two-point (2 and 6 hr or 0 and 2 hr) sampling strategy. RESULTS: A simplified strategy with three time points of blood collection at 0, 1, and 3 hours after CsA-ME allowed adequate and accurate prediction of the daily exposure to CsA. AUC prediction with two-point sampling at 2 and 6 hours 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 2 hour time points were examined, in which only 51% of AUC estimates were included in the accepted range of variation (-10 to 10%). CONCLUSIONS: A limited strategy of three-point sampling taken early after dosing allows an excellent and perfectly reliable prediction of the actual AUC.
Authors: Surajith N Wanasundara; Michal J Wesolowski; Mark C Barnfield; Michael L Waller; Anthony W Murray; Maria T Burniston; Paul S Babyn; Carl A Wesolowski Journal: Nucl Med Commun Date: 2016-01 Impact factor: 1.690