(BQ) Part 2 book “Translational admet for drug therapy - Principles, methods, and pharmaceutical applications” has contents: Drug drug interaction - from bench to drug label, general toxicology, toxicokinetics and toxicity testing in drug development, translational tools toward better drug therapy in human populations, and other contents. | 5 DRUG–DRUG INTERACTION: FROM BENCH TO DRUG LABEL INTRODUCTION: THE IMPACT OF DRUG–DRUG INTERACTION ON DRUG DISPOSITION AND DRUG SAFETY Drug–drug interaction (DDI) is one of the major obstacles for the pharmaceutical drug development process; uncovering its potential on any adverse clinical outcomes becomes increasingly important in drug discovery and development. Both in vitro and in vivo preclinical investigations to assess the any clinical outcomes prior to drug launch are taken into account to reveal the potential of DDI and its mechanism of any drug under development. Evaluation of the possible interactions of a drug candidate with other drugs as soon as possible—not only as an inhibitor or inducer (perpetrator) but also as a substrate (victim)—could avoid detrimental DDIs in humans. As will be discussed later, DDIs represent a major mechanism of adverse drug reactions, and consequently their evaluation is critical to studies within all the drug development stages, drug discovery, and regulation of new drug candidates to avoid any serious toxicity that leads to drug withdrawal postmarket. Finally, the ultimate goal of nonclinical and clinical DDI studies is to permit integration of DDI knowledge acquired in the development phase into prescribing guidance in a manner that enables optimal postmarketing risk management following marketing authorization. Not all the preclinically determined DDIs can be considered as clinically significant (poor correlation between in vitro and in vivo observation). The systemic Translational ADMET for Drug Therapy: Principles, Methods, and Pharmaceutical Applications, First Edition. Souzan B. Yanni. © 2015 John Wiley & Sons, Inc. Published 2015 by John Wiley & Sons, Inc. 140 DRUG–DRUG INTERACTION: FROM BENCH TO DRUG LABEL Victim Drug Absorption and Metabolism Perpetrator Drug [Inducer] Perpetrator Drug [Inhibitor] Hi exposure and toxicity Low renal/biliary excretion Low exposure and efficacy High .
