Meta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents

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 0-336 h compared with 0-24 h. 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 EditorIn 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.

Graphical AbstractPlasma Concentration-vs.-Time Profiles of Encapsulated S-CKD602 at 2.10 mg/m2 IV × 1 and NL-CDK602 at 0.50 mg/m2 IV × 1. This manuscript evaluates the differences in inter-patient PK variability of liposomal and non-liposomal formulations of anticancer agents, from which we have determined that PK variability of liposomal agents is significantly greater than small molecule non-liposomal agents.Figure optionsDownload high-quality image (198 K)Download as PowerPoint slide