Interpatient Pharmacokinetic and Pharmacodynamic Variability of Carrier‐Mediated Anticancer Agents

@article{Caron2012InterpatientPA,
  title={Interpatient Pharmacokinetic and Pharmacodynamic Variability of Carrier‐Mediated Anticancer Agents},
  author={Whitney P. Caron and Gina Song and P. Kiran Kumar and Sumit Rawal and William C. Zamboni},
  journal={Clinical Pharmacology \& Therapeutics},
  year={2012},
  volume={91}
}
Major advances in the field of carrier‐mediated agents (CMAs) have revolutionized drug delivery capabilities over the past decade. While providing numerous advantages over their small‐molecule counterparts (solubility, duration of exposure, and delivery to the site of action are higher), these agents display substantial variability in systemic clearance (CL) and distribution, tumor delivery, and pharmacologic effects. This review provides an overview of factors that affect the pharmacokinetics… 
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61 Citations

The effects of nanoparticle drug loading on the pharmacokinetics of anticancer agents.
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This review provides an overview of factors that affect the pharmacokinetics and pharmacodynamics of carrier-mediated agents in preclinical models and patients.
Complex effects of tumor microenvironment on the tumor disposition of carrier-mediated agents.
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An overview of tumor microenvironment factors that affect the pharmacokinetics and pharmacodynamics of carrier-mediated agents observed in preclinical models and patients are provided.
Formulation and physiologic factors affecting the pharmacology of carrier-mediated anticancer agents
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An overview of factors that affect the pharmacologic profiles observed in CMA-formulated chemotherapy, primarily in liposomal formulations, that are currently in preclinical or early clinical development are provided.
Challenges in preclinical to clinical translation for anticancer carrier-mediated agents.
TLDR
Future studies are warranted to better understand the complex pharmacology and interaction of CMA carriers within individual preclinical models and their biological systems, such as the MPS and tumor microenvironment, and their application to allometric scaling across species.
Methods and Study Designs for Characterizing the Pharmacokinetics and Pharmacodynamics of Carrier-Mediated Agents.
TLDR
This chapter focuses on the analytical and phenotypic methods required to design a study that characterizes the pharmacokinetics (PK) and pharmacodynamics (PD) of all forms of these nanoparticle-based drug agents.
Complex Factors and Challenges that Affect the Pharmacology, Safety and Efficacy of Nanocarrier Drug Delivery Systems
TLDR
This review aims to provide a summary of fundamental factors that affect the disposition of NPs in the treatment of cancer and why they should be evaluated during preclinical and clinical development.
Pharmacokinetic and Pharmacodynamic Aspects of Focal and Targeted Delivery of Drugs
TLDR
The major pharmacokinetic and pharmacodynamic parameters that govern the clinical effectiveness of systemically and focally administered DDSs are presented, and the ways to control the drug/DDSs disposition and the efficiency of the pharmacological responses are discussed.
Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology.
TLDR
This report summarizes the workshop discussions on key issues of the EPR effect and major gaps that need to be addressed to effectively advance nanoparticle-based drug delivery.
Evaluation of the efficiency of tumor and tissue delivery of carrier-mediated agents (CMA) and small molecule (SM) agents in mice using a novel pharmacokinetic (PK) metric: relative distribution index over time (RDI-OT)
TLDR
In mice bearing flank tumor xenografts, SMs distribute into tumor more efficiently than CMAs, and a novel PK metric entitled relative distribution over time (RDI-OT), which measures efficiency of delivery is indicated.
Recent Advances in Tumor Targeting via EPR Effect for Cancer Treatment
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This review will address in detail the progress and prospects of tumor-targeting via EPR effect for cancer therapy.
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