Role of equilibrative nucleoside transporter 1 (ENT1) in the disposition of cytarabine in mice
Abstract Cytarabine (Ara‐C) is a nucleoside analog used in the treatment of acute myeloid leukemia (AML). Despite the many years of clinical use, the identity of the transporter(s) involved in the disposition of Ara‐C remains poorly studied. Previous work demonstrated that concurrent administration...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-12-01
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| Series: | Pharmacology Research & Perspectives |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/prp2.534 |
| _version_ | 1818848618604396544 |
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| author | Jason T. Anderson Shuiying Hu Qiang Fu Sharyn D. Baker Alex Sparreboom |
| author_facet | Jason T. Anderson Shuiying Hu Qiang Fu Sharyn D. Baker Alex Sparreboom |
| author_sort | Jason T. Anderson |
| collection | DOAJ |
| description | Abstract Cytarabine (Ara‐C) is a nucleoside analog used in the treatment of acute myeloid leukemia (AML). Despite the many years of clinical use, the identity of the transporter(s) involved in the disposition of Ara‐C remains poorly studied. Previous work demonstrated that concurrent administration of Ara‐C with nitrobenzylmercaptopurine ribonucleoside (NBMPR) causes an increase in Ara‐C plasma levels, suggesting involvement of one or more nucleoside transporters. Here, we confirmed the presence of an NMBPR‐mediated interaction with Ara‐C resulting in a 2.5‐fold increased exposure. The interaction was unrelated to altered blood cell distribution, and subsequent studies indicated that the disposition of Ara‐C was unaffected in mice with a deficiency of postulated candidate transporters, including ENT1, OCTN1, OATP1B2, and MATE1. These studies indicate the involvement of an unknown NBMPR‐sensitive Ara‐C transporter that impacts the pharmacokinetic properties of this clinically important agent. |
| first_indexed | 2024-12-19T06:20:12Z |
| format | Article |
| id | doaj.art-6e004fa2425f495d8f5c0c835326c642 |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-12-19T06:20:12Z |
| publishDate | 2019-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-6e004fa2425f495d8f5c0c835326c6422022-12-21T20:32:44ZengWileyPharmacology Research & Perspectives2052-17072019-12-0176n/an/a10.1002/prp2.534Role of equilibrative nucleoside transporter 1 (ENT1) in the disposition of cytarabine in miceJason T. Anderson0Shuiying Hu1Qiang Fu2Sharyn D. Baker3Alex Sparreboom4Division of Pharmaceutics and Pharmacology College of Pharmacy and Comprehensive Cancer Center The Ohio State University Columbus OH USADivision of Pharmaceutics and Pharmacology College of Pharmacy and Comprehensive Cancer Center The Ohio State University Columbus OH USADivision of Pharmaceutics and Pharmacology College of Pharmacy and Comprehensive Cancer Center The Ohio State University Columbus OH USADivision of Pharmaceutics and Pharmacology College of Pharmacy and Comprehensive Cancer Center The Ohio State University Columbus OH USADivision of Pharmaceutics and Pharmacology College of Pharmacy and Comprehensive Cancer Center The Ohio State University Columbus OH USAAbstract Cytarabine (Ara‐C) is a nucleoside analog used in the treatment of acute myeloid leukemia (AML). Despite the many years of clinical use, the identity of the transporter(s) involved in the disposition of Ara‐C remains poorly studied. Previous work demonstrated that concurrent administration of Ara‐C with nitrobenzylmercaptopurine ribonucleoside (NBMPR) causes an increase in Ara‐C plasma levels, suggesting involvement of one or more nucleoside transporters. Here, we confirmed the presence of an NMBPR‐mediated interaction with Ara‐C resulting in a 2.5‐fold increased exposure. The interaction was unrelated to altered blood cell distribution, and subsequent studies indicated that the disposition of Ara‐C was unaffected in mice with a deficiency of postulated candidate transporters, including ENT1, OCTN1, OATP1B2, and MATE1. These studies indicate the involvement of an unknown NBMPR‐sensitive Ara‐C transporter that impacts the pharmacokinetic properties of this clinically important agent.https://doi.org/10.1002/prp2.534acute myeloid leukemiacytarabineENT1NBMPROCTN1transporters |
| spellingShingle | Jason T. Anderson Shuiying Hu Qiang Fu Sharyn D. Baker Alex Sparreboom Role of equilibrative nucleoside transporter 1 (ENT1) in the disposition of cytarabine in mice Pharmacology Research & Perspectives acute myeloid leukemia cytarabine ENT1 NBMPR OCTN1 transporters |
| title | Role of equilibrative nucleoside transporter 1 (ENT1) in the disposition of cytarabine in mice |
| title_full | Role of equilibrative nucleoside transporter 1 (ENT1) in the disposition of cytarabine in mice |
| title_fullStr | Role of equilibrative nucleoside transporter 1 (ENT1) in the disposition of cytarabine in mice |
| title_full_unstemmed | Role of equilibrative nucleoside transporter 1 (ENT1) in the disposition of cytarabine in mice |
| title_short | Role of equilibrative nucleoside transporter 1 (ENT1) in the disposition of cytarabine in mice |
| title_sort | role of equilibrative nucleoside transporter 1 ent1 in the disposition of cytarabine in mice |
| topic | acute myeloid leukemia cytarabine ENT1 NBMPR OCTN1 transporters |
| url | https://doi.org/10.1002/prp2.534 |
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