Model-Based Evaluation of HangAmDan-B1 and Afatinib Combination Therapy in HCC827 Xenograft Mice with Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor
<b>Objectives:</b> HangAmDan-B1 (HAD-B1), a blended herbal mixture, has been investigated as an adjuvant therapy with afatinib (AFT) to treat non-small lung cancer (NSCLC). Although preclinical studies demonstrated promising synergistic results, clinical trials have not yet confirmed the...
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2025-05-01
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| author | Sung-yoon Yang Lien Thi Ngo Soyoung Lee Hwi-yeol Yun Tham Thi Bui Dong-Hyeon Kim Jung-woo Chae Sojung Park |
| author_facet | Sung-yoon Yang Lien Thi Ngo Soyoung Lee Hwi-yeol Yun Tham Thi Bui Dong-Hyeon Kim Jung-woo Chae Sojung Park |
| author_sort | Sung-yoon Yang |
| collection | DOAJ |
| description | <b>Objectives:</b> HangAmDan-B1 (HAD-B1), a blended herbal mixture, has been investigated as an adjuvant therapy with afatinib (AFT) to treat non-small lung cancer (NSCLC). Although preclinical studies demonstrated promising synergistic results, clinical trials have not yet confirmed the expected benefits. This study aims to quantitatively examine the exposure–response relationship and synergistic interactions through pharmacokinetic/pharmacodynamic (PK/PD) modeling. <b>Methods:</b> A PK/PD model was established and validated based on tumor growth profiles from a xenograft mouse study of gefitinib-resistant HCC827. Model-based simulations were performed to predict and assess therapeutic effects across different treatment groups. <b>Results:</b> The PK/PD model confirmed HAD-B1 enhances the potency of AFT by 1.45-fold. Model-based simulations predicted that combination treatment maintains a lower tumor size compared to AFT monotherapy. <b>Conclusions:</b> This study quantitatively demonstrated the synergistic interaction between HAD-B1 and AFT. The developed PK/PD model provides insights into potential dosing strategies to treat NSCLC resistant to EGFR-TKIs. Further clinical trials are warranted to validate these findings and refine dosing strategies to improve therapeutic outcomes. |
| format | Article |
| id | doaj-art-c0b6b81acb9e4a7587ef5eff8a937faa |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj-art-c0b6b81acb9e4a7587ef5eff8a937faa2025-08-20T03:47:58ZengMDPI AGPharmaceuticals1424-82472025-05-0118574810.3390/ph18050748Model-Based Evaluation of HangAmDan-B1 and Afatinib Combination Therapy in HCC827 Xenograft Mice with Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase InhibitorSung-yoon Yang0Lien Thi Ngo1Soyoung Lee2Hwi-yeol Yun3Tham Thi Bui4Dong-Hyeon Kim5Jung-woo Chae6Sojung Park7College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaFaculty of Pharmacy, PHENIKAA University, Yen Nghia, Ha Dong, Hanoi 12116, VietnamCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaDepartment of Internal Medicine, Pusan National University, Korean Medicine Hospital, Yangsan 50612, Republic of KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaDepartment of Internal Medicine, Pusan National University, Korean Medicine Hospital, Yangsan 50612, Republic of Korea<b>Objectives:</b> HangAmDan-B1 (HAD-B1), a blended herbal mixture, has been investigated as an adjuvant therapy with afatinib (AFT) to treat non-small lung cancer (NSCLC). Although preclinical studies demonstrated promising synergistic results, clinical trials have not yet confirmed the expected benefits. This study aims to quantitatively examine the exposure–response relationship and synergistic interactions through pharmacokinetic/pharmacodynamic (PK/PD) modeling. <b>Methods:</b> A PK/PD model was established and validated based on tumor growth profiles from a xenograft mouse study of gefitinib-resistant HCC827. Model-based simulations were performed to predict and assess therapeutic effects across different treatment groups. <b>Results:</b> The PK/PD model confirmed HAD-B1 enhances the potency of AFT by 1.45-fold. Model-based simulations predicted that combination treatment maintains a lower tumor size compared to AFT monotherapy. <b>Conclusions:</b> This study quantitatively demonstrated the synergistic interaction between HAD-B1 and AFT. The developed PK/PD model provides insights into potential dosing strategies to treat NSCLC resistant to EGFR-TKIs. Further clinical trials are warranted to validate these findings and refine dosing strategies to improve therapeutic outcomes.https://www.mdpi.com/1424-8247/18/5/748pharmacokinetic/pharmacodynamic modelingafatinibhangamdan-B1non-small cell lung cancerEGFR-TKI resistancedrug–drug interactions |
| spellingShingle | Sung-yoon Yang Lien Thi Ngo Soyoung Lee Hwi-yeol Yun Tham Thi Bui Dong-Hyeon Kim Jung-woo Chae Sojung Park Model-Based Evaluation of HangAmDan-B1 and Afatinib Combination Therapy in HCC827 Xenograft Mice with Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Pharmaceuticals pharmacokinetic/pharmacodynamic modeling afatinib hangamdan-B1 non-small cell lung cancer EGFR-TKI resistance drug–drug interactions |
| title | Model-Based Evaluation of HangAmDan-B1 and Afatinib Combination Therapy in HCC827 Xenograft Mice with Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor |
| title_full | Model-Based Evaluation of HangAmDan-B1 and Afatinib Combination Therapy in HCC827 Xenograft Mice with Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor |
| title_fullStr | Model-Based Evaluation of HangAmDan-B1 and Afatinib Combination Therapy in HCC827 Xenograft Mice with Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor |
| title_full_unstemmed | Model-Based Evaluation of HangAmDan-B1 and Afatinib Combination Therapy in HCC827 Xenograft Mice with Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor |
| title_short | Model-Based Evaluation of HangAmDan-B1 and Afatinib Combination Therapy in HCC827 Xenograft Mice with Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor |
| title_sort | model based evaluation of hangamdan b1 and afatinib combination therapy in hcc827 xenograft mice with resistance to epidermal growth factor receptor tyrosine kinase inhibitor |
| topic | pharmacokinetic/pharmacodynamic modeling afatinib hangamdan-B1 non-small cell lung cancer EGFR-TKI resistance drug–drug interactions |
| url | https://www.mdpi.com/1424-8247/18/5/748 |
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