http://csmres.co.uk/cs.public.upd/article-downloads/Slingerland_2012_Drug-Discovery-Today.pdf

Liposomal drug formulations in cancer therapy: 15 years along the road.

Various attempts to increase the therapeutic index of the drug while minimizing side effects have been made in drug delivery systems. Among several promising strategies, liposomes represent an advanced technology to target active molecules to the site of action. Rapid clearance of circulating liposomal drugs administered intravenously has been a critical issue because circulation time in the blood affects drug exposure at the target site. The clinical use of liposomal drugs is complicated by large intra- and interindividual variability in their pharmacokinetics (PK) and pharmacodynamics (PD). Thus, it is important to understand the factors affecting the PK/PD of the liposomal formulation of drugs and to elucidate the mechanisms underlying the variability in the PK/PD of liposomal drugs. In this review article, we describe the characteristics of liposome formulations and discuss the effects of various factors, including liposome-associated factors, host-associated factors, and treatment on the PK/PD of liposomal agents.

Factors affecting the pharmacokinetics and pharmacodynamics of liposomal drugs.

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 (PK) and pharmacodynamics (PD) of CMAs in preclinical models and patients.

Clinical Pharmacology & Therapeutics (2012); 91 5, 802–812. doi:10.1038/clpt.2012.12

Interpatient Pharmacokinetic and Pharmacodynamic Variability of Carrier-Mediated Anticancer Agents

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

Developing nanoparticles to improve the specificity of anticancer agents towards tumor tissues and to better control drug delivery is a rising strategy in oncology. An increasing number of forms (e.g., conjugated nanoparticles, liposomes, immunoliposomes…) are now made available on the shelves and numerous other scaffolds (e.g., dendrimeres, nanospheres, squalenes…) are currently at various stages of development. However, the attrition rate when developing nanoparticles is particularly high and several promising forms showing excellent behavior and efficacy in preclinical studies failed to succeed in subsequent first-in-man studies or later in phase-II trials. The issue of pharmacokinetic variability is a major, yet largely underestimated issue with nanoparticles. A wide variety of causes (e.g; tumor type and disease staging, comorbidities, patient’s immune system) can explain this variability, which can in return impact negatively on pharmacodynamic endpoints such as lack of efficacy or severe toxicities. This review aims at covering the main causes for erratic pharmacokinetics observed with most nanoparticles. Should the main causes of such variability be identified, specific studies in non-clinical or clinical development stages could be undertaken using dedicated models (i.e., mechanistic or semi-mechanistic mathematical models such as PBPK approaches) to better describe nanoparticles pharmacokinetics and decipher PK/PD relationships. In addition, identifying relevant biomarkers or parameters likely to impact on nanoparticles pharmacokinetics would allow either modifying their characteristics to reduce the influence of the expected variability during development phases, or developing biomarker-based adaptive dosing strategies to maintain an optimal efficacy/toxicity balance. Overall, we call of developing comprehensive distribution studies and state-of-the-art modeling support to help better picture and anticipate nanoparticles pharmacokinetics.

/pdf/pharmacokinetics-variability-why-nanoparticles-are-not-just-3whhyjnjae.pdf

Pharmacokinetics variability: Why nanoparticles are not just magic-bullets in oncology

e13003 Background: Peglyated liposomal (PL) anticancer agents are nanoparticles that may improve antitumor efficacy by enhancing tumor drug delivery while limiting exposure in normal tissues. Howev...

The evaluation of gender on the pharmacokinetics (PK) of pegylated liposomal anticancer agents.

2547 Background: Irinotecan (CPT-11) is a prodrug of SN-38 that has antitumor activity in a wide range of solid tumors. IHL- 305 is a PEGylated-liposomal formulation of irinotecan designed to increase the therapeutic index by prolonging the duration of exposure in both plasma and tumors. IHL-305 demonstrates superior anti-tumor activity in preclinical models. Methods: Eligible patients (pts) had advanced solid tumors, ECOG ≤2, adequate organ function and no prior exposure to CPT-11. In a standard 3+3 escalation, IHL-305 was infused over 60 minutes q 28 days. UGT1A1*28 genotyping was performed with the homozygous (*28/*28) variants treated at 50% of current dose (subsequent escalation allowed). The area under the plasma concentration- time curve (AUC) of sum total (encapsulated + released) CPT-11, released CPT-11, SN-38, and SN-38 glucuronide (SN-38G) was calculated. The % CPT-11 released was calculated as the ratio of released CPT-11 AUC to sum total CPT-11 AUC x 100. The primary objectives were to determ...

Phase I and pharmacokinetic (PK) study of IHL-305 (pegylated liposomal irinotecan) in patients with advanced solid tumors

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

S. Ikeda

Author Tools

Chat about Author

Papers

The evaluation of gender on the pharmacokinetics (PK) of pegylated liposomal anticancer agents.

Phase I and pharmacokinetic (PK) study of IHL-305 (pegylated liposomal irinotecan) in patients with advanced solid tumors