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Effect of phenobarbital on plasma levels of cyclophosphamide and its metabolites in the mouse.

We have studied the quantitative pharmacokinetic differences of individual metabolites and unchanged cyclophosphamide (CPA) in control and phenobarbital-treated animals, using radiolabelled CPA together with thin-layer chromatography. On Day 0, one group was started on phenobarbital drinking water a...

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Autores principales: Alberts, D. S., Peng, Y. M., Chen, H. S., Struck, R. F.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1978
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2009716/
https://www.ncbi.nlm.nih.gov/pubmed/698048
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author Alberts, D. S.
Peng, Y. M.
Chen, H. S.
Struck, R. F.
author_facet Alberts, D. S.
Peng, Y. M.
Chen, H. S.
Struck, R. F.
author_sort Alberts, D. S.
collection PubMed
description We have studied the quantitative pharmacokinetic differences of individual metabolites and unchanged cyclophosphamide (CPA) in control and phenobarbital-treated animals, using radiolabelled CPA together with thin-layer chromatography. On Day 0, one group was started on phenobarbital drinking water and one group stayed on regular acid water. P388 leukaemia, (10(6) cells i.p.) was administered to all mice on Day 8, and 2 days later both groups of mice were given i.p. CPA (200 mg/kg) with 14C-CPA (0.2 muCi per mouse). At 5--60 min after CPA administration, groups of 10 mice were killed and their blood collected for assay of parent compound and metabolites in plasma. Phenobarbital pretreatment reduced CPA and phosphoramide mustard CXT (concentration x time) by 66+% and 27+%, respectively. Assuming that phosphoramide mustard is both the ultimate cytotoxic form of CPA and the blood-transport form, the reduction of CPA by phenobarbital would predict a decreased therapeutic effect. The assay methods in this study will be used in the future to determine the importance of this potential drug interaction in man.
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spelling pubmed-20097162009-09-10 Effect of phenobarbital on plasma levels of cyclophosphamide and its metabolites in the mouse. Alberts, D. S. Peng, Y. M. Chen, H. S. Struck, R. F. Br J Cancer Research Article We have studied the quantitative pharmacokinetic differences of individual metabolites and unchanged cyclophosphamide (CPA) in control and phenobarbital-treated animals, using radiolabelled CPA together with thin-layer chromatography. On Day 0, one group was started on phenobarbital drinking water and one group stayed on regular acid water. P388 leukaemia, (10(6) cells i.p.) was administered to all mice on Day 8, and 2 days later both groups of mice were given i.p. CPA (200 mg/kg) with 14C-CPA (0.2 muCi per mouse). At 5--60 min after CPA administration, groups of 10 mice were killed and their blood collected for assay of parent compound and metabolites in plasma. Phenobarbital pretreatment reduced CPA and phosphoramide mustard CXT (concentration x time) by 66+% and 27+%, respectively. Assuming that phosphoramide mustard is both the ultimate cytotoxic form of CPA and the blood-transport form, the reduction of CPA by phenobarbital would predict a decreased therapeutic effect. The assay methods in this study will be used in the future to determine the importance of this potential drug interaction in man. Nature Publishing Group 1978-08 /pmc/articles/PMC2009716/ /pubmed/698048 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
Alberts, D. S.
Peng, Y. M.
Chen, H. S.
Struck, R. F.
Effect of phenobarbital on plasma levels of cyclophosphamide and its metabolites in the mouse.
title Effect of phenobarbital on plasma levels of cyclophosphamide and its metabolites in the mouse.
title_full Effect of phenobarbital on plasma levels of cyclophosphamide and its metabolites in the mouse.
title_fullStr Effect of phenobarbital on plasma levels of cyclophosphamide and its metabolites in the mouse.
title_full_unstemmed Effect of phenobarbital on plasma levels of cyclophosphamide and its metabolites in the mouse.
title_short Effect of phenobarbital on plasma levels of cyclophosphamide and its metabolites in the mouse.
title_sort effect of phenobarbital on plasma levels of cyclophosphamide and its metabolites in the mouse.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2009716/
https://www.ncbi.nlm.nih.gov/pubmed/698048
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