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Effects of Apigenin on Pharmacokinetics of Dasatinib and Probable Interaction Mechanism
Dasatinib (DAS), a narrow-therapeutic index drug, Bcr-Abl, and Src family kinases multitarget inhibitor have been approved for chronic myelogenous leukemia (CML) and Ph-positive acute lymphocytic leukemia (Ph+ ALL). Apigenin (APG) has a long history of human usage in food, herbs, health supplements,...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9964503/ https://www.ncbi.nlm.nih.gov/pubmed/36838589 http://dx.doi.org/10.3390/molecules28041602 |
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author | Raish, Mohammad Ahmad, Ajaz Shahid, Mudassar Jardan, Yousef A. Bin Ahad, Abdul Kalam, Mohd Abul Ansari, Mushtaq Ahmad Iqbal, Muzaffar Ali, Naushad Alkharfy, Khalid M. Al-Jenoobi, Fahad I. |
author_facet | Raish, Mohammad Ahmad, Ajaz Shahid, Mudassar Jardan, Yousef A. Bin Ahad, Abdul Kalam, Mohd Abul Ansari, Mushtaq Ahmad Iqbal, Muzaffar Ali, Naushad Alkharfy, Khalid M. Al-Jenoobi, Fahad I. |
author_sort | Raish, Mohammad |
collection | PubMed |
description | Dasatinib (DAS), a narrow-therapeutic index drug, Bcr-Abl, and Src family kinases multitarget inhibitor have been approved for chronic myelogenous leukemia (CML) and Ph-positive acute lymphocytic leukemia (Ph+ ALL). Apigenin (APG) has a long history of human usage in food, herbs, health supplements, and traditional medicine, and it poses low risk of damage. The concomitant use of APG containing herbs/foods and traditional medicine may alter the pharmacokinetics of DAS, that probably lead to possible herb–drug interactions. The pharmacokinetic interaction of APG pretreatment with DAS in rat plasma following single and co-oral dosing was successfully deliberated using the UPLC–MS/MS method. The in vivo pharmacokinetics and protein expression of CYP3A2, Pgp-MDR1, and BCPR/ABCG2 demonstrate that APG pretreatment has potential to drastically changed the DAS pharmacokinetics where escalation in the Cmax, AUC((0–t)), AUMC((0-inf_obs)), T(1/2), Tmax, and MRT and reduction in Kel, Vd, and Cl significantly in rats pretreated with APG 40 mg/kg, thus escalating systemic bioavailability and increasing the rate of absorption via modulation of CYP3A2, Pgp-MDR1, and BCPR/ABCG2 protein expression. Therefore, the concomitant consumption of APG containing food or traditional herb with DAS may cause serious life-threatening drug interactions and more systematic clinical study on herb–drug interactions is required, as well as adequate regulation in herbal safety and efficacy. |
format | Online Article Text |
id | pubmed-9964503 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99645032023-02-26 Effects of Apigenin on Pharmacokinetics of Dasatinib and Probable Interaction Mechanism Raish, Mohammad Ahmad, Ajaz Shahid, Mudassar Jardan, Yousef A. Bin Ahad, Abdul Kalam, Mohd Abul Ansari, Mushtaq Ahmad Iqbal, Muzaffar Ali, Naushad Alkharfy, Khalid M. Al-Jenoobi, Fahad I. Molecules Article Dasatinib (DAS), a narrow-therapeutic index drug, Bcr-Abl, and Src family kinases multitarget inhibitor have been approved for chronic myelogenous leukemia (CML) and Ph-positive acute lymphocytic leukemia (Ph+ ALL). Apigenin (APG) has a long history of human usage in food, herbs, health supplements, and traditional medicine, and it poses low risk of damage. The concomitant use of APG containing herbs/foods and traditional medicine may alter the pharmacokinetics of DAS, that probably lead to possible herb–drug interactions. The pharmacokinetic interaction of APG pretreatment with DAS in rat plasma following single and co-oral dosing was successfully deliberated using the UPLC–MS/MS method. The in vivo pharmacokinetics and protein expression of CYP3A2, Pgp-MDR1, and BCPR/ABCG2 demonstrate that APG pretreatment has potential to drastically changed the DAS pharmacokinetics where escalation in the Cmax, AUC((0–t)), AUMC((0-inf_obs)), T(1/2), Tmax, and MRT and reduction in Kel, Vd, and Cl significantly in rats pretreated with APG 40 mg/kg, thus escalating systemic bioavailability and increasing the rate of absorption via modulation of CYP3A2, Pgp-MDR1, and BCPR/ABCG2 protein expression. Therefore, the concomitant consumption of APG containing food or traditional herb with DAS may cause serious life-threatening drug interactions and more systematic clinical study on herb–drug interactions is required, as well as adequate regulation in herbal safety and efficacy. MDPI 2023-02-07 /pmc/articles/PMC9964503/ /pubmed/36838589 http://dx.doi.org/10.3390/molecules28041602 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Raish, Mohammad Ahmad, Ajaz Shahid, Mudassar Jardan, Yousef A. Bin Ahad, Abdul Kalam, Mohd Abul Ansari, Mushtaq Ahmad Iqbal, Muzaffar Ali, Naushad Alkharfy, Khalid M. Al-Jenoobi, Fahad I. Effects of Apigenin on Pharmacokinetics of Dasatinib and Probable Interaction Mechanism |
title | Effects of Apigenin on Pharmacokinetics of Dasatinib and Probable Interaction Mechanism |
title_full | Effects of Apigenin on Pharmacokinetics of Dasatinib and Probable Interaction Mechanism |
title_fullStr | Effects of Apigenin on Pharmacokinetics of Dasatinib and Probable Interaction Mechanism |
title_full_unstemmed | Effects of Apigenin on Pharmacokinetics of Dasatinib and Probable Interaction Mechanism |
title_short | Effects of Apigenin on Pharmacokinetics of Dasatinib and Probable Interaction Mechanism |
title_sort | effects of apigenin on pharmacokinetics of dasatinib and probable interaction mechanism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9964503/ https://www.ncbi.nlm.nih.gov/pubmed/36838589 http://dx.doi.org/10.3390/molecules28041602 |
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