Abstract
Recently, the resistance of trastuzumab as an established monoclonal antibody therapy for women with breast cancers overexpressing human epithelial growth factor receptor 2 (HER2) has been issued and the activation of phosphoinositide 3‐kinase (PI3K) pathway was identified as a main mechanism of resistance. As the combinations of western and oriental medicines have emerged accompanying the improvement of efficacy and/or safety in chemotherapies, the cases for combinations of trastuzumab and oriental medicines has been reported. H9 is a formula of nine medicinal herbs derived from Osuyubujaijung‐tang, a traditional Korean prescription for Soeumin constitution, targeting HER2‐PI3K/Akt pathway and consequently showing anticancer effects against breast cancer and lung cancer in vitro and in vivo. The synergistic effect of trastuzumab and H9 combination was reported in vivo mice model of lung cancers. Regarding that the current drug interaction issues of therapeutic proteins including monoclonal antibody with small molecules, the effect of H9 on pharmacokinetic interaction of trastuzumab in aspect of systemic exposure and tissue distribution was investigated in this study. Prior to evaluation of pharmacokinetic interaction of trastuzumab with H9, the analytical method of trastuzumab using ELISA was validated.In the validation of ELISA analytical method, 0.1–20 mg/mL of trastuzumab were analysed showing below 13.8% of precision and 84.3–112% accuracy values, respectively. In pharmacokinetics, H9 did not change any pharmacokinetic parameters of trastuzumab and also there was no difference on tissue distribution of trastuzumab to liver, heart, lung, and spleen in trastuzumab and H9 combinations. These results provided an evidence for the development of this combination therapy in clinical levels after the further investigations of dosage regimen adjustments.Support or Funding InformationThis study was supported by National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIT) (NRF‐2016R1C1B2010849 and NRF‐2018R15A2023217).
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
