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Reduced exposure of imatinib after coadministration with acetaminophen in mice
PURPOSE: Imatinib is an efficacious drug against chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST) due to selective inhibition of c-KIT and BCR-ABL kinases. It presents almost complete bioavailability, is eliminated via P450-mediated metabolism and is well tolerated. However,...
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Formato: | Texto |
Lenguaje: | English |
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Medknow Publications
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875735/ https://www.ncbi.nlm.nih.gov/pubmed/20523867 http://dx.doi.org/10.4103/0253-7613.56071 |
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author | Nassar, Inthisham Pasupati, Thanikachalam Judson, John Paul Segarra, Ignacio |
author_facet | Nassar, Inthisham Pasupati, Thanikachalam Judson, John Paul Segarra, Ignacio |
author_sort | Nassar, Inthisham |
collection | PubMed |
description | PURPOSE: Imatinib is an efficacious drug against chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST) due to selective inhibition of c-KIT and BCR-ABL kinases. It presents almost complete bioavailability, is eliminated via P450-mediated metabolism and is well tolerated. However, a few severe drug-drug interactions have been reported in cancer patients taking acetaminophen. MATERIALS AND METHODS: Male ICR mice were given 100 mg/kg single dose of imatinib orally or imatinib 100 mg/kg (orally) coadministered with acetaminophen intraperitoneally (700 mg/kg). Mice were euthanized at predetermined time points, blood samples collected, and imatinib plasma concentration measured by HPLC. RESULTS: Imatinib AUC(0-12) was 27.04 ± 0.38 mg·h/ml, C(max) was 7.21 ± 0.99 mg/ml and elimination half-life was 2.3 hours. Acetaminophen affected the imatinib disposition profile: AUC(0-12) and C(max) decreased 56% and 59%, respectively and a longer half-life was observed (5.6 hours). CONCLUSIONS: The study shows a pharmacokinetic interaction between acetaminophen and imatinib which may render further human studies necessary if both drugs are administered concurrently to cancer patients. |
format | Text |
id | pubmed-2875735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Medknow Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-28757352010-06-03 Reduced exposure of imatinib after coadministration with acetaminophen in mice Nassar, Inthisham Pasupati, Thanikachalam Judson, John Paul Segarra, Ignacio Indian J Pharmacol Research Article PURPOSE: Imatinib is an efficacious drug against chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST) due to selective inhibition of c-KIT and BCR-ABL kinases. It presents almost complete bioavailability, is eliminated via P450-mediated metabolism and is well tolerated. However, a few severe drug-drug interactions have been reported in cancer patients taking acetaminophen. MATERIALS AND METHODS: Male ICR mice were given 100 mg/kg single dose of imatinib orally or imatinib 100 mg/kg (orally) coadministered with acetaminophen intraperitoneally (700 mg/kg). Mice were euthanized at predetermined time points, blood samples collected, and imatinib plasma concentration measured by HPLC. RESULTS: Imatinib AUC(0-12) was 27.04 ± 0.38 mg·h/ml, C(max) was 7.21 ± 0.99 mg/ml and elimination half-life was 2.3 hours. Acetaminophen affected the imatinib disposition profile: AUC(0-12) and C(max) decreased 56% and 59%, respectively and a longer half-life was observed (5.6 hours). CONCLUSIONS: The study shows a pharmacokinetic interaction between acetaminophen and imatinib which may render further human studies necessary if both drugs are administered concurrently to cancer patients. Medknow Publications 2009-08 /pmc/articles/PMC2875735/ /pubmed/20523867 http://dx.doi.org/10.4103/0253-7613.56071 Text en © Indian Journal of Pharmacology http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Nassar, Inthisham Pasupati, Thanikachalam Judson, John Paul Segarra, Ignacio Reduced exposure of imatinib after coadministration with acetaminophen in mice |
title | Reduced exposure of imatinib after coadministration with acetaminophen in mice |
title_full | Reduced exposure of imatinib after coadministration with acetaminophen in mice |
title_fullStr | Reduced exposure of imatinib after coadministration with acetaminophen in mice |
title_full_unstemmed | Reduced exposure of imatinib after coadministration with acetaminophen in mice |
title_short | Reduced exposure of imatinib after coadministration with acetaminophen in mice |
title_sort | reduced exposure of imatinib after coadministration with acetaminophen in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875735/ https://www.ncbi.nlm.nih.gov/pubmed/20523867 http://dx.doi.org/10.4103/0253-7613.56071 |
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