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,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/4/1602 |
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| author | Mohammad Raish Ajaz Ahmad Mudassar Shahid Yousef A. Bin Jardan Abdul Ahad Mohd Abul Kalam Mushtaq Ahmad Ansari Muzaffar Iqbal Naushad Ali Khalid M. Alkharfy Fahad I. Al-Jenoobi |
| author_facet | Mohammad Raish Ajaz Ahmad Mudassar Shahid Yousef A. Bin Jardan Abdul Ahad Mohd Abul Kalam Mushtaq Ahmad Ansari Muzaffar Iqbal Naushad Ali Khalid M. Alkharfy Fahad I. Al-Jenoobi |
| author_sort | Mohammad Raish |
| collection | DOAJ |
| 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<sub>(0–t)</sub>, AUMC<sub>(0-inf_obs)</sub>, T<sub>1/2</sub>, Tmax, and MRT and reduction in K<i>el</i>, 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. |
| first_indexed | 2024-03-11T08:21:56Z |
| format | Article |
| id | doaj.art-34e02e397d7542a8be7e7e80346539cb |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T08:21:56Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-34e02e397d7542a8be7e7e80346539cb2023-11-16T22:20:43ZengMDPI AGMolecules1420-30492023-02-01284160210.3390/molecules28041602Effects of Apigenin on Pharmacokinetics of Dasatinib and Probable Interaction MechanismMohammad Raish0Ajaz Ahmad1Mudassar Shahid2Yousef A. Bin Jardan3Abdul Ahad4Mohd Abul Kalam5Mushtaq Ahmad Ansari6Muzaffar Iqbal7Naushad Ali8Khalid M. Alkharfy9Fahad I. Al-Jenoobi10Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaQuality Assurance Unit, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDasatinib (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<sub>(0–t)</sub>, AUMC<sub>(0-inf_obs)</sub>, T<sub>1/2</sub>, Tmax, and MRT and reduction in K<i>el</i>, 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.https://www.mdpi.com/1420-3049/28/4/1602dasatinibsinapic acidherb drug interactionsPgP/MDR1BCPR/ABCG2CYP3A2 |
| spellingShingle | Mohammad Raish Ajaz Ahmad Mudassar Shahid Yousef A. Bin Jardan Abdul Ahad Mohd Abul Kalam Mushtaq Ahmad Ansari Muzaffar Iqbal Naushad Ali Khalid M. Alkharfy Fahad I. Al-Jenoobi Effects of Apigenin on Pharmacokinetics of Dasatinib and Probable Interaction Mechanism Molecules dasatinib sinapic acid herb drug interactions PgP/MDR1 BCPR/ABCG2 CYP3A2 |
| 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 | dasatinib sinapic acid herb drug interactions PgP/MDR1 BCPR/ABCG2 CYP3A2 |
| url | https://www.mdpi.com/1420-3049/28/4/1602 |
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