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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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Autores principales: Nassar, Inthisham, Pasupati, Thanikachalam, Judson, John Paul, Segarra, Ignacio
Formato: Texto
Lenguaje:English
Publicado: Medknow Publications 2009
Materias:
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.
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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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