Abstract: In order to improve the efficacy or reduce the side effects, the combination of two or more drugs is often used in clinical practice, which often brings new medication problems that change the process or efficacy of a drug in vivo due to combination. This article reviews the clinical drug-drug interaction (DDI) researches of 44 novel molecular entities which were approved to be launched in China from January 2000 to March 2021. Among them, clinical DDI trials based on test drugs as substrates of the metabolic enzymes (11/44) especially as the substrates of CYP3A4 (7/11) are dominant. The results show that most of test drugs were CYP3A4 substrates with a moderate or lower sensitivity, and no highly sensitive substrates were found. The second is the clinical DDI trials based on synergy or reducing side effects, which mainly focus on the fields of tumors, diabetes, and viral infections, and these studies have not shown pharmacokinetic interactions with clinical significance. The DDI trials of test drugs as metabolic enzyme modulators account for 7/44. And transporter-based DDI trials are relatively rare and most of them are in vitro studies. With the in-depth study of drug metabolism/transport mechanisms in vivo and in vitro, especially the development of clinical trials of radioisotope-labeled drugs and computer simulations, the overall level of DDI research in China is gradually improving, which will provide a solid scientific foundation to ensure drug safety.

Key words: innovative small molecule drugs, clinical drug-drug interactions, metabolic enzymes, transporters