A phase I study on the reversal of multidrug resistance (MDR) in vivo: nifedipine plus etoposide.

Multidrug resistance (MDR) is one of the mechanisms of resistance to multiple cytotoxic drugs and is mediated by the expression of a membrane pump called the P-glycoprotein. Nifedipine is one of the calcium channel blocking agents which reverses MDR in vitro. Fifteen patients with various malignanci...

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Autores principales: Philip, P. A., Joel, S., Monkman, S. C., Dolega-Ossowski, E., Tonkin, K., Carmichael, J., Idle, J. R., Harris, A. L.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1992
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977739/
https://www.ncbi.nlm.nih.gov/pubmed/1739628
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author Philip, P. A.
Joel, S.
Monkman, S. C.
Dolega-Ossowski, E.
Tonkin, K.
Carmichael, J.
Idle, J. R.
Harris, A. L.
author_facet Philip, P. A.
Joel, S.
Monkman, S. C.
Dolega-Ossowski, E.
Tonkin, K.
Carmichael, J.
Idle, J. R.
Harris, A. L.
author_sort Philip, P. A.
collection PubMed
description Multidrug resistance (MDR) is one of the mechanisms of resistance to multiple cytotoxic drugs and is mediated by the expression of a membrane pump called the P-glycoprotein. Nifedipine is one of the calcium channel blocking agents which reverses MDR in vitro. Fifteen patients with various malignancies received nifedipine at three dose levels: 40 mg, 60 mg and 80 mg orally twice daily for 6 days. Etoposide was administered intravenously on day 2 in a dose of 150-250 mg m-2 and orally 150-300 mg twice daily on days 3 and 4. Cardiovascular effects of nifedipine were dose limiting and the maximum tolerated dose was 60 mg bid. Mean area under the plasma concentration curve (AUC0-00) and plasma half-life (beta) of nifedipine and its major metabolite MI at the highest dose level were 7.87 microM.h, 7.97 h and 4.97 microM.h, 14.0 h respectively. Nifedipine did not interfere with the pharmacokinetics of etoposide.
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spelling pubmed-19777392009-09-10 A phase I study on the reversal of multidrug resistance (MDR) in vivo: nifedipine plus etoposide. Philip, P. A. Joel, S. Monkman, S. C. Dolega-Ossowski, E. Tonkin, K. Carmichael, J. Idle, J. R. Harris, A. L. Br J Cancer Research Article Multidrug resistance (MDR) is one of the mechanisms of resistance to multiple cytotoxic drugs and is mediated by the expression of a membrane pump called the P-glycoprotein. Nifedipine is one of the calcium channel blocking agents which reverses MDR in vitro. Fifteen patients with various malignancies received nifedipine at three dose levels: 40 mg, 60 mg and 80 mg orally twice daily for 6 days. Etoposide was administered intravenously on day 2 in a dose of 150-250 mg m-2 and orally 150-300 mg twice daily on days 3 and 4. Cardiovascular effects of nifedipine were dose limiting and the maximum tolerated dose was 60 mg bid. Mean area under the plasma concentration curve (AUC0-00) and plasma half-life (beta) of nifedipine and its major metabolite MI at the highest dose level were 7.87 microM.h, 7.97 h and 4.97 microM.h, 14.0 h respectively. Nifedipine did not interfere with the pharmacokinetics of etoposide. Nature Publishing Group 1992-02 /pmc/articles/PMC1977739/ /pubmed/1739628 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
Philip, P. A.
Joel, S.
Monkman, S. C.
Dolega-Ossowski, E.
Tonkin, K.
Carmichael, J.
Idle, J. R.
Harris, A. L.
A phase I study on the reversal of multidrug resistance (MDR) in vivo: nifedipine plus etoposide.
title A phase I study on the reversal of multidrug resistance (MDR) in vivo: nifedipine plus etoposide.
title_full A phase I study on the reversal of multidrug resistance (MDR) in vivo: nifedipine plus etoposide.
title_fullStr A phase I study on the reversal of multidrug resistance (MDR) in vivo: nifedipine plus etoposide.
title_full_unstemmed A phase I study on the reversal of multidrug resistance (MDR) in vivo: nifedipine plus etoposide.
title_short A phase I study on the reversal of multidrug resistance (MDR) in vivo: nifedipine plus etoposide.
title_sort phase i study on the reversal of multidrug resistance (mdr) in vivo: nifedipine plus etoposide.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977739/
https://www.ncbi.nlm.nih.gov/pubmed/1739628
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