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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.

Original publication

DOI

10.1038/bjc.1992.53

Type

Journal article

Journal

Br J Cancer

Publication Date

02/1992

Volume

65

Pages

267 - 270

Keywords

Administration, Oral, Adult, Aged, Drug Administration Schedule, Drug Evaluation, Drug Interactions, Drug Resistance, Etoposide, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Neoplasms, Nifedipine