25 August 2026
Humanized Liver Mouse Models for Predicting Human Drug Metabolism and DDI
Drug development requires preclinical evaluation to determine the safety profile and potential efficacy, which includes understanding how a compound is absorbed, distributed, metabolized, and excreted (ADME). However, even with preclinical studies, around 80~90% of drug candidates will fail to make it to the market.1, 2 The top reasons for failure include: 1. toxicity (30%), 2. ineffectiveness (40~50%), and 3. reduced ADME (10~15%).2 Animal models are used to predict human ADME and safety profiles however, these studies do not always correlate to clinical findings and often overestimate the potential of drug candidates.3, 4 Given this low success rate, it is important to understand the driving factors that lead to drug failure. Here, we will discuss how species-specific differences in metabolism might contribute to the failed clinical success of drug candidates. Then, we will introduce the humanized liver mouse model and other alternative preclinical models that can better predict clinical success.