Evaluation of the potential herb-drug interaction between Bojungikki-tang and PD-L1 immunotherapy in a syngeneic mouse model

• Published in: Frontiers in pharmacology Vol. 14; p. 1181263
• Main Authors: Yang, Sung-Yoon, Yi, Jin-Mu, Chun, Jaemoo, Park, Seongwon, Bui, Tham Thi, Yun, Hwi-Yeol, Chae, Jung-Woo, Jeong, Mi-Kyung
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 18-05-2023
• Subjects: atezolizumab; Bojungikki-tang; CMT-167; drug-drug interaction; PD-L1; Pharmacology; PD-L1; atezolizumab; CMT-167; drug-drug interaction; Bojungikki-tang
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2023.1181263

Atezolizumab (a PD-L1 inhibitor) has shown remarkable efficacy and tolerability in various cancer types. Despite its efficacy and safety, atezolizumab monotherapy has limitations, such as acquired resistance and adverse events. Bojungikki-tang (BJIKT) is an herbal decoction widely prescribed in Asian countries and used to treat cancer-related symptoms including fatigue, appetite loss, gastrointestinal disorders, and other side effects from cancer therapy. Due to its immunomodulatory effects, Bojungikki-tang has been investigated as a combined treatment with anticancer agents. We evaluated the potential drug-drug interaction (DDI) between Bojungikki-tang and the anti-PD-L1 antibody based on the Food and Drug Administration (FDA) guidelines. In the study, we conducted an
drug-drug interaction study using a syngeneic mouse model of CMT-167 in C57BL/6. We then determined the antibody concentrations to evaluate the pharmacokinetic (PK) drug-drug interaction and measured variable biomarkers related to therapeutic efficacy and immune response. The pharmacodynamic (PD) drug-drug interaction study investigated changes in response between anti-PD-L1 antibody monotherapy and combination therapy. Using the pharmacokinetic and pharmacodynamic data, we conducted a statistical analysis to assess drug-drug interaction potential. In the presence of Bojungikki-tang, the pharmacokinetic characteristics of the anti-PD-L1 antibody were not changed. This study suggested that combination treatment with Bojungikki-tang and atezolizumab is a safe treatment option for non-small cell lung cancer. Clinical studies are warranted to confirm this finding.