Open AccessA phase I study on the reversal of multidrug resistance (MDR) in vivo: nifedipine plus etoposide
Author(s) -
P. A. Philip,
S. Joel,
S. C. Monkman,
E. Dolega-Ossowski,
Katia Tonkin,
J. Carmichael,
J R Idle,
Adrian L. Harris
Publication year - 1992
Publication title -
british journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.833
H-Index - 236
eISSN - 1532-1827
pISSN - 0007-0920
DOI - 10.1038/bjc.1992.53
Subject(s) - nifedipine , etoposide , pharmacology , pharmacokinetics , in vivo , medicine , multiple drug resistance , metabolite , chemistry , chemotherapy , calcium , biology , antibiotics , biochemistry , microbiology and biotechnology
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.