Meta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents
Nanomedicine: Nanotechnology, Biology, and Medicine
CKD-602, Liposomes, Pharmacokinetic, S-CKD602, Sampling schema, Variability
A meta-analysis was conducted to evaluate the inter-patient pharmacokinetic (PK) variability of liposomal and small molecule (SM) anticancer agents. Inter-patient PK variability of 9 liposomal and SM formulations of the same drug was evaluated. PK variability was measured as coefficient of variance (CV%) of area under the plasma concentration versus time curve (AUC) and the fold-difference between AUCmax and AUCmin (AUC range). CV% of AUC and AUC ranges were 2.7-fold (P<0.001) and 16.7-fold (P=0.13) greater, respectively, for liposomal compared with SM drugs. There was an inverse linear relationship between the clearance (CL) of liposomal agents and PK variability with a lower CL associated with greater PK variability (R2=0.39). PK variability of liposomal agents was greater when evaluated from 0-336h compared with 0-24h. PK variability of liposomes is significantly greater than SM. The factors associated with the PK variability of liposomal agents need to be evaluated. From the Clinical Editor: In this meta-analysis, the inter-patient pharmacokinetic variability of 9 liposomal and small molecule anti-cancer agents was studied. The authors determined that several parameters are in favor of the liposomal formulation; however, the PK variability of the formulation was higher compared with small molecule agents, the reason for which remains to be determined in future studies. © 2014.
Schell, R., Sidone, B., Caron, W., Walsh, M., White, T., Zamboni, B., Ramanathan, R., & Zamboni, W. (2014). Meta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents. Nanomedicine: Nanotechnology, Biology, and Medicine, 10 (1), 109-117. https://doi.org/10.1016/j.nano.2013.07.005