Webinar: Plasma Protein Binding in Drug Development
Sponsored by: Covance
Focused on:
Date: 6th November
Days old: 4474
Time: 8AM PST / 10AM CST / 11AM EST / 4PM GMT
Regulatory Expectations, Special Considerations and Application to Clinical Development
Plasma protein binding is a physico-chemical interaction between a drug and various proteins commonly present in plasma. At equilibrium, a percentage of the total drug concentration is bound to plasma proteins with the remaining present as unbound drug often referred to as the free fraction. Current theory proposes that only the free fraction of a circulating drug is available to interact with the drug target, enter cells and undergo further metabolism and elimination.
Therefore, the free fraction of drug in plasma is a critical component in the assessment of clinical pharmacokinetics and pharmacodynamics, and is a parameter that could contribute to clinically relevant drug-drug interactions or safety pharmacology issues. As a result, regulatory authorities strongly recommend a determination of the free fraction prior to commencement of Phase I human trials. Whilst determination of protein binding may seem relatively simple and straightforward, recent publications have highlighted the complexities of the methodology and indicate the need to control temperature and pH in order to provide meaningful data.
Moreover, while nonclinical in vitro free fraction determination is valid to support initial Phase I clinical studies in healthy human populations, phase II studies in disease state populations (such as those with hepatic or renal impairment) require a tailored protocol. Here we discuss some of the regulatory expectations regarding assessment of plasma protein binding, as well as present approaches to control pH, temperature and determine free fraction in disease state populations.
Presented by
Peter Kilford, PhD,
Study Director, Drug Metabolism, Covance Harrogate
After training as a Biochemist, Peter then started a PhD in 2005 at the Centre for Applied Pharmackinetic Research at the University of Manchester, where he focused on the in vitro prediction of drug glucuronidation clearance. In 2009, after completion of his PhD, Peter joined Covance Laboratories in Harrogate, UK where he now works as an in vitro Study Director. Peter has specialised in techniques such as in vitro protein binding, drug-drug interactions and phase II drug metabolism. Over the course of his career, Peter has produced a number of publications and also presented at international conferences. More recently Peter has focused on the improvement of protein binding techniques at Covance.
David Erickson,
Study Director, Drug Metabolism, Covance Madison
David joined Covance in 2001 as a study director overseeing in vitro metabolism studies and has served in this capacity for over 11 years. During this time, David developed extensive expertise in plasma protein binding and has established dependable methodology for the measurement of the free fraction of drugs in association with clinical studies, particularly those involving special populations.
Prior to joining Covance, David was cumulatively employed for over 20 years by the US Dept of the Interior, the Medical College of Wisconsin, Boehringer Ingelheim Pharmaceuticals, and Absorption Systems serving as a toxicologist and a metabolism scientist. David’s expertise includes significant research contributions in support of IND and NDA filings with the FDA
Download Slides
Please login to download the slidesKey Learning Objectives
- Understand general aspects of protein binding and it’s role in the disposition of drugs
- Understand global regulatory perspectives
- Learn about the role and importance of pH control
- Learn about an optimized approach when conducting clinical studies involving disease state populations
Audience
- CEO/President/Chairman/Executive Director
- Pharmaceutical Companies
- Corporate Management
- Senior R&D/Lab R&D
- Therapeutic Area Leaders