TY - JOUR T1 - How Current Understanding of Clearance Mechanisms and Pharmacodynamics of Therapeutic Proteins Can Be Applied for Evaluation of Their Drug-Drug Interaction Potential JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1779 LP - 1783 DO - 10.1124/dmd.111.040808 VL - 39 IS - 10 AU - Eugenia Kraynov AU - Steven W. Martin AU - Susan Hurst AU - Odette A. Fahmi AU - Martin Dowty AU - Carol Cronenberger AU - Cho-Ming Loi AU - Bing Kuang AU - Owen Fields AU - Scott Fountain AU - Michel Awwad AU - Diane Wang Y1 - 2011/10/01 UR - http://dmd.aspetjournals.org/content/39/10/1779.abstract N2 - Increasing use of therapeutic proteins (TPs) in polypharmacy settings calls for more in-depth understanding of the biological interactions that can lead to increased toxicity or loss of pharmacological effect. Factors such as patient population, medications that are likely to be coadministered in that population, clearance mechanisms of a TP, and concomitant drugs have to be taken into account to determine the potential for drug-drug interactions (DDIs). The most well documented TP DDI mechanism involves cytokine-mediated changes in drug-metabolizing enzymes. Because of the limitations of the current preclinical models for addressing this type of DDI, clinical evaluation is currently the most reliable approach. Other DDI mechanisms need to be addressed on a case-by-case basis. These include altered clearance of TPs resulting from the changes in the target protein levels by the concomitant medication, displacement of TPs from binding proteins, modulation of Fcγ receptor expression, and others. The purpose of this review is to introduce the approach used by Pfizer scientists for evaluation of the DDI potential of novel TP products during drug discovery and development. ER -