Physiologically based pharmacokinetic modeling of imatinib and N ‐desmethyl imatinib for drug–drug interaction predictions
AbstractThe first-generation tyrosine kinase inhibitor imatinib has revolutionized the development of targeted cancer therapy and remains among the frontline treatments, for example, against chronic myeloid leukemia. As a substrate of cytochrome P450 (CYP) 2C8, CYP3A4, and various transporters, imatinib is highly susceptible to drug –drug interactions (DDIs) when co-administered with corresponding perpetrator drugs. Additionally, imatinib and its main metaboliteN-desmethyl imatinib (NDMI) act as inhibitors of CYP2C8, CYP2D6, and CYP3A4 affecting their own metabolism as well as the exposure of co-medications. This work pr...
Source: CPT: Pharmacometrics and Systems Pharmacology - March 14, 2024 Category: Drugs & Pharmacology Authors: Helena Leonie Hanae Loer,
Christina Kovar,
Simeon R üdesheim,
Fatima Zahra Marok,
Laura Maria Fuhr,
Dominik Selzer,
Matthias Schwab,
Thorsten Lehr Tags: ARTICLE Source Type: research
Imatinib plus Cetuximab as a Window of Opportunity Clinical Trial in Head and Neck Cancer
Cetuximab, an approved anti-EGFR receptor monoclonal antibody, is used for the treatment of metastatic cancer, often in conjunction with cytotoxic chemotherapy. It is also employed as a radiosensitizer in the context of definitive radiation therapy for locally advanced cases. However, overcoming resistance to cetuximab, whether intrinsic or acquired, represents a significant challenge in clinical practice. In preclinical studies, the identification of tyrosine 821 (Y821) on the C-terminal of AXL has been linked to resistance to both cetuximab and radiation therapy via signaling through the tyrosine kinase c-Abl. (Source: I...
Source: International Journal of Radiation Oncology * Biology * Physics - March 14, 2024 Category: Radiology Authors: J.Y. Bruce, T. Glazer, M. Iida, B. Mehall, K.L. Kostecki, M. Yu, A. Wieland, G.K. Hartig, T.M. McCulloch, D. Trask, A. Burr, P.M. Harari, R.J. Kimple, D.L. Wheeler Tags: 223 Source Type: research
ERS/EBMT clinical practice guideline on treatment of pulmonary chronic graft- < em > versus < /em > -host disease in adults
Eur Respir J. 2024 Mar 14:2301727. doi: 10.1183/13993003.01727-2023. Online ahead of print.ABSTRACTChronic graft-versus-host disease (cGvHD) is a common complication after allogeneic haematopoietic stem cell transplantation, characterised by a broad disease spectrum that can affect virtually any organ. Although pulmonary cGvHD is a less common manifestation, it is of great concern due to its severity and poor prognosis. Optimal management of patients with pulmonary cGvHD is complicated and no standardised approach is available.The purpose of this joint European Respiratory Society and European Society for Blood and Marrow ...
Source: Respiratory Care - March 14, 2024 Category: Respiratory Medicine Authors: Saskia Bos John Murray Monia Marchetti Guang-Shing Cheng Anne Bergeron Daniel Wolff Clare Sander Akshay Sharma Sherif M Badawy Zinaida Peric Agnieszka Piekarska Joseph Pidala Kavita Raj Olaf Penack Samar Kulkarni Molly Beestrum Andrea Linke Matthew Rutter Source Type: research
A safety review of tyrosine kinase inhibitors for chronic myeloid leukemia
Expert Opin Drug Saf. 2024 Mar 14. doi: 10.1080/14740338.2024.2331190. Online ahead of print.ABSTRACTINTRODUCTION: Since the introduction of first tyrosine kinase inhibitor(TKI) imatinib, treatment of chronic myeloid leukemia (CML) has reachedexcellent survival expectancies. Long survival rates bring about issuesregarding TKI safety.AREAS COVERED: The aim of this review is to compare the side effectsof current TKIs both in the first- and later lines and outline a safety andprofile of CML treatment. Seminal studies on TKIs and other newer drugs andextended follow-up of these studies, real-life data of each drug were useddur...
Source: Expert Opinion on Drug Safety - March 14, 2024 Category: Drugs & Pharmacology Authors: Deniz Özmen Duygu Demet Alpayd ın Muhammed Ali Saldo ğan Ahmet Emre E şkazan Source Type: research
Physiologically based pharmacokinetic modeling of imatinib and N ‐desmethyl imatinib for drug–drug interaction predictions
AbstractThe first-generation tyrosine kinase inhibitor imatinib has revolutionized the development of targeted cancer therapy and remains among the frontline treatments, for example, against chronic myeloid leukemia. As a substrate of cytochrome P450 (CYP) 2C8, CYP3A4, and various transporters, imatinib is highly susceptible to drug –drug interactions (DDIs) when co-administered with corresponding perpetrator drugs. Additionally, imatinib and its main metaboliteN-desmethyl imatinib (NDMI) act as inhibitors of CYP2C8, CYP2D6, and CYP3A4 affecting their own metabolism as well as the exposure of co-medications. This work pr...
Source: CPT: Pharmacometrics and Systems Pharmacology - March 14, 2024 Category: Drugs & Pharmacology Authors: Helena Leonie Hanae Loer,
Christina Kovar,
Simeon R üdesheim,
Fatima Zahra Marok,
Laura Maria Fuhr,
Dominik Selzer,
Matthias Schwab,
Thorsten Lehr Tags: ARTICLE Source Type: research
Tyrosine kinase inhibitor –induced hypothyroidism: mechanism and clinical implications
DiscussionThis review discusses the epidemiology, possible mechanisms, and clinical significance of hypothyroidism in cancer patients treated with TKI. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - March 14, 2024 Category: Drugs & Pharmacology Source Type: research
Progressive hyperpigmentation and lentigines due to KIT variants improving with imatinib
Br J Dermatol. 2024 Mar 12:ljae109. doi: 10.1093/bjd/ljae109. Online ahead of print.NO ABSTRACTPMID:38470964 | DOI:10.1093/bjd/ljae109 (Source: The British Journal of Dermatology)
Source: The British Journal of Dermatology - March 12, 2024 Category: Dermatology Authors: Lina Liang Sha Peng Shimiao Huang Huijun Wang Zhimiao Lin Source Type: research
Targeting oncogenic kinases: Insights on FDA approved tyrosine kinase inhibitors
Eur J Pharmacol. 2024 Mar 9:176484. doi: 10.1016/j.ejphar.2024.176484. Online ahead of print.ABSTRACTProtein kinases play pivotal roles in various biological functions, influencing cell differentiation, promoting survival, and regulating the cell cycle. The disruption of protein kinase activity is intricately linked to pathways in tumor development. This manuscript explores the transformative impact of protein kinase inhibitors on cancer therapy, particularly their efficacy in cases driven by targeted mutations. Focusing on key tyrosine kinase inhibitors (TKIs) like Bcr-Abl, Epidermal Growth Factor Receptor (EGFR), and Vas...
Source: European Journal of Pharmacology - March 11, 2024 Category: Drugs & Pharmacology Authors: Sahil Hussain Mohd Mursal Garima Verma Syed Misbahul Hasan Mohemmed Faraz Khan Source Type: research
Targeting oncogenic kinases: Insights on FDA approved tyrosine kinase inhibitors
Eur J Pharmacol. 2024 Mar 9:176484. doi: 10.1016/j.ejphar.2024.176484. Online ahead of print.ABSTRACTProtein kinases play pivotal roles in various biological functions, influencing cell differentiation, promoting survival, and regulating the cell cycle. The disruption of protein kinase activity is intricately linked to pathways in tumor development. This manuscript explores the transformative impact of protein kinase inhibitors on cancer therapy, particularly their efficacy in cases driven by targeted mutations. Focusing on key tyrosine kinase inhibitors (TKIs) like Bcr-Abl, Epidermal Growth Factor Receptor (EGFR), and Vas...
Source: European Journal of Pharmacology - March 11, 2024 Category: Drugs & Pharmacology Authors: Sahil Hussain Mohd Mursal Garima Verma Syed Misbahul Hasan Mohemmed Faraz Khan Source Type: research
Targeting oncogenic kinases: Insights on FDA approved tyrosine kinase inhibitors
Eur J Pharmacol. 2024 Mar 9:176484. doi: 10.1016/j.ejphar.2024.176484. Online ahead of print.ABSTRACTProtein kinases play pivotal roles in various biological functions, influencing cell differentiation, promoting survival, and regulating the cell cycle. The disruption of protein kinase activity is intricately linked to pathways in tumor development. This manuscript explores the transformative impact of protein kinase inhibitors on cancer therapy, particularly their efficacy in cases driven by targeted mutations. Focusing on key tyrosine kinase inhibitors (TKIs) like Bcr-Abl, Epidermal Growth Factor Receptor (EGFR), and Vas...
Source: European Journal of Pharmacology - March 11, 2024 Category: Drugs & Pharmacology Authors: Sahil Hussain Mohd Mursal Garima Verma Syed Misbahul Hasan Mohemmed Faraz Khan Source Type: research
Comparison of the Efficacy Among Nilotinib, Dasatinib, Flumatinib and Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia Patients: A Real-World Multi-Center Retrospective Study
CONCLUSION: Nilotinib, dasatinib and flumatinib had comparable efficacy, and significantly higher therapy responses and higher FFS rates than imatinib in newly diagnosed CML patients. However, there were no significant differences in PFS and OS among these 4 TKIs. These real-world data may provide additional evidence for routine clinical assessments to identify more appropriate therapies.PMID:38461040 | DOI:10.1016/j.clml.2024.02.008 (Source: Clinical Lymphoma and Myeloma)
Source: Clinical Lymphoma and Myeloma - March 9, 2024 Category: Cancer & Oncology Authors: Xiaoshuai Zhang Na Xu Yunfan Yang Hai Lin Bingcheng Liu Xin Du Xiaoli Liu Rong Liang Chunyan Chen Jian Huang Huanling Zhu Ling Pan Xiaodong Wang Guohui Li Zhuogang Liu Yanqing Zhang Zhenfang Liu Jianda Hu Chunshui Liu Fei Li Wei Yang Li Meng Yanqiu Han Li Source Type: research
