Research ArticleMeta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents
Graphical Abstract
Plasma 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.
Section snippets
Systematic review and meta-analysis
To directly compare interpatient PK variability of multiple liposomal and non-liposomal anticancer agents, a systematic review and a meta-analysis were conducted utilizing PubMed (1966-2011) and manual searches of reference sections of key articles. Phase I and II studies that included PK studies were included in our analysis. The systematic review yielded 9 liposomal and non-liposomal formulations of the same anticancer agents. A complete list of evaluated agents with a brief description of
Meta-analysis of PK variability
We compared inter-patient PK variability differences of corresponding liposomal and non-liposomal anticancer agents at similar doses. Figure 1 represents the plasma concentration versus time profiles of liposomal and non-liposomal CKD-602, one of the 9 agents evaluated in the meta-analysis. Here, each agent was administered to 6 patients at the respective MTD (S-CKD602 at 2.10 mg/m2 and NL-CKD602 at 0.5 mg/m2). Visual inspection reveals a tighter grouping of profiles between patients administered
Discussion
High inter-patient PK variability observed with many anticancer agents makes it difficult to predict a patient’s response to a particular drug. Moreover, liposomes often report higher PK variability compared with small molecules and non-liposomal agents, further clouding predictions of outcomes associated with these carrier agents. We comprehensively evaluated these differences in a meta-analysis of 9 liposomal and non-liposomal anticancer agents. This is the first meta-analysis evaluating the
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