A phase I study on the reversal of multidrug resistance (MDR) in vivo: nifedipine plus etoposide: Clinical Oncology/Epidemiology

A phase I study on the reversal of multidrug resistance (MDR) in vivo: nifedipine plus etoposide: Clinical Oncology/Epidemiology

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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Veröffentlicht in:British journal of cancer 1992-02, Vol.65 (2), p.267-270
Hauptverfasser: Philip, PA, Joel, S, Monkman, SC, Dolega-Ossowski, E, Tonkin, K, Carmichael, J, Idle, JR, Harris, AL
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Biomedical and Life Sciences
Biomedicine
Cancer Research
clinical-oncology-epidemiology
Drug Resistance
Epidemiology
Molecular Medicine
Oncology
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container_end_page 270
container_issue 2
container_start_page 267
container_title British journal of cancer
container_volume 65
creator Philip, PA
Joel, S
Monkman, SC
Dolega-Ossowski, E
Tonkin, K
Carmichael, J
Idle, JR
Harris, AL
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.
doi_str_mv 10.1038/bjc.1992.53
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subjects Biomedical and Life Sciences
Biomedicine
Cancer Research
clinical-oncology-epidemiology
Drug Resistance
Epidemiology
Molecular Medicine
Oncology
title A phase I study on the reversal of multidrug resistance (MDR) in vivo: nifedipine plus etoposide: Clinical Oncology/Epidemiology
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