AAPS Workshop Report: Strategies to Address Therapeutic Protein–Drug Interactions during Clinical Development
Journal Title: The AAPS Journal - Year 2011, Vol 13, Issue 3
Abstract
Therapeutic proteins (TPs) are increasingly combined with small molecules and/or with other TPs. However preclinical tools and in vitro test systems for assessing drug interaction potential of TPs such as monoclonal antibodies, cytokines and cytokine modulators are limited. Published data suggests that clinically relevant TP-drug interactions (TP-DI) are likely from overlap in mechanisms of action, alteration in target and/or drug-disease interaction. Clinical drug interaction studies are not routinely conducted for TPs because of the logistical constraints in study design to address pharmacokinetic (PK)- and pharmacodynamic (PD)-based interactions. Different pharmaceutical companies have developed their respective question- and/or risk-based approaches for TP-DI based on the TP mechanism of action as well as patient population. During the workshop both company strategies and regulatory perspectives were discussed in depth using case studies; knowledge gaps and best practices were subsequently identified and discussed. Understanding the functional role of target, target expression and their downstream consequences were identified as important for assessing the potential for a TP-DI. Therefore, a question-and/or risk-based approach based upon the mechanism of action and patient population was proposed as a reasonable TP-DI strategy. This field continues to evolve as companies generate additional preclinical and clinical data to improve their understanding of possible mechanisms for drug interactions. Regulatory agencies are in the process of updating their recommendations to sponsors regarding the conduct of in vitro and in vivo interaction studies for new drug applications (NDAs) and biologics license applications (BLAs).
Authors and Affiliations
Sandhya Girish, Steven W Martin, Mark C Peterson, Lei K. Zhang, Hong Zhao, Joseph Balthasar, Raymond Evers, Honghui Zhou, Min Zhu, Lewis Klunk, Chao Han, Eva Gil Berglund, Shiew-Mei Huang, Amita Joshi
Keywords
Related Articles
- EP ID EP681334
- DOI 10.1208/s12248-011-9285-6
- Views 81
- Downloads 0
Electronic and resonance effects on the lonization of structural analogues of efavirenz
The solubility of 4 analogues of efavirenz was studied as a function of pH. The study evaluated the ionization behavior and determined the relative contribution of electronegative substituents versus resonance effects on...
Utilizing Internal Standard Responses to Assess Risk on Reporting Bioanalytical Results from Hemolyzed Samples
Bioanalytical analysis of toxicokinetic and pharmacokinetic samples is an integral part of small molecule drugs development and liquid chromatography—tandem mass spectrometry (LC-MS/MS) has been the technique of...
Comparison of Intestinal Absorption and Disposition of Structurally Similar Bioactive Flavones in Radix Scutellariae
Radix Scutellariae is a commonly used herbal medicine. Baicalein, wogonin, and oroxylin A are three major bioactive flavones in Radix Scutellariae and share similar chemical structures. The intestinal absorption and disp...
Versatility of Particulate Carriers: Development of Pharmacodynamically Optimized Drug-Loaded Microparticles for Treatment of Peritoneal Cancer
Intraperitoneal (IP) chemotherapy confers significant survival benefits in cancer patients. However, several problems, including local toxicity and ineffectiveness against bulky tumors, have prohibited it from becoming a...
Pharmacogenomics: The promise of personalized medicine