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British Journal of Cancer logoLink to British Journal of Cancer
. 1987 Aug;56(2):119–122. doi: 10.1038/bjc.1987.167

Amiodarone is more efficient than verapamil in reversing resistance to anthracyclines in tumour cells.

B Chauffert 1, D Rey 1, B Coudert 1, M Dumas 1, F Martin 1
PMCID: PMC2002148  PMID: 3663463

Abstract

We have previously demonstrated that amiodarone is able to reverse resistance of rat colon cancer cells to anthracyclines. We now compare the efficiency of amiodarone to verapamil one, another antiarrhythmic agent used in experimental systems and in clinical trials to enhance the effects of anthracyclines on resistant cancer cells. Amiodarone is more efficient than verapamil when both drugs are used at the same molar concentrations. Desethylamiodarone, the main metabolite of amiodarone, is as efficient as its precursor. Optimal concentrations of amiodarone are obtained without side effects in the sera of patients treated by oral administration followed by a loading infusion of amiodarone. On the other hand, maximal tolerated levels of verapamil reported in clinical trials are less efficient than amiodarone maximal levels in the reversal of resistance to anthracyclines in our experimental model in vitro. We suggest that amiodarone, which is more efficient and less toxic than verapamil, could be substituted for verapamil in future clinical trials.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andreasen F., Agerbaek H., Bjerregaard P., Gøtzsche H. Pharmacokinetics of amiodarone after intravenous and oral administration. Eur J Clin Pharmacol. 1981 Mar;19(4):293–299. doi: 10.1007/BF00562807. [DOI] [PubMed] [Google Scholar]
  2. Benson A. B., 3rd, Trump D. L., Koeller J. M., Egorin M. I., Olman E. A., Witte R. S., Davis T. E., Tormey D. C. Phase I study of vinblastine and verapamil given by concurrent iv infusion. Cancer Treat Rep. 1985 Jul-Aug;69(7-8):795–799. [PubMed] [Google Scholar]
  3. Chauffert B., Martin F., Caignard A., Jeannin J. F., Leclerc A. Cytofluorescence localization of adriamycin in resistant colon cancer cells. Cancer Chemother Pharmacol. 1984;13(1):14–18. doi: 10.1007/BF00401439. [DOI] [PubMed] [Google Scholar]
  4. Chauffert B., Martin M., Hammann A., Michel M. F., Martin F. Amiodarone-induced enhancement of doxorubicin and 4'-deoxydoxorubicin cytotoxicity to rat colon cancer cells in vitro and in vivo. Cancer Res. 1986 Feb;46(2):825–830. [PubMed] [Google Scholar]
  5. Inaba M., Kobayashi H., Sakurai Y., Johnson R. K. Active efflux of daunorubicin and adriamycin in sensitive and resistant sublines of P388 leukemia. Cancer Res. 1979 Jun;39(6 Pt 1):2200–2203. [PubMed] [Google Scholar]
  6. Lubbe W. F., Mercer C. J. Amiodarone: its side effects, adverse reactions and dosage schedules. N Z Med J. 1982 Jul 28;95(712):502–504. [PubMed] [Google Scholar]
  7. Martin F., Caignard A., Olsson O., Jeannin J. F., Leclerc A. Tumoricidal effect of macrophages exposed to adriamycin in vivo or in vitro. Cancer Res. 1982 Sep;42(9):3851–3857. [PubMed] [Google Scholar]
  8. Martin F., Knobel S., Martin M., Bordes M. A carcinofetal antigen located on the membrane of cells from rat intestinal carcinoma in culture. Cancer Res. 1975 Feb;35(2):333–336. [PubMed] [Google Scholar]
  9. Mostow N. D., Rakita L., Vrobel T. R., Noon D., Blumer J. Amiodarone: intravenous loading for rapid suppression of complex ventricular arrhythmias. J Am Coll Cardiol. 1984 Jul;4(1):97–104. doi: 10.1016/s0735-1097(84)80325-3. [DOI] [PubMed] [Google Scholar]
  10. Pourbaix S., Berger Y., Desager J. P., Pacco M., Harvengt C. Absolute bioavailability of amiodarone in normal subjects. Clin Pharmacol Ther. 1985 Feb;37(2):118–123. doi: 10.1038/clpt.1985.22. [DOI] [PubMed] [Google Scholar]
  11. Reiter M. J., Shand D. G., Aanonsen L. M., Wagoner R., McCarthy E., Pritchett E. L. Pharmacokinetics of verapamil: experience with a sustained intravenous infusion regimen. Am J Cardiol. 1982 Oct;50(4):716–721. doi: 10.1016/0002-9149(82)91224-3. [DOI] [PubMed] [Google Scholar]
  12. Rogan A. M., Hamilton T. C., Young R. C., Klecker R. W., Jr, Ozols R. F. Reversal of adriamycin resistance by verapamil in human ovarian cancer. Science. 1984 Jun 1;224(4652):994–996. doi: 10.1126/science.6372095. [DOI] [PubMed] [Google Scholar]
  13. Singh B. N., Ellrodt G., Peter C. T. Verapamil: a review of its pharmacological properties and therapeutic use. Drugs. 1978 Mar;15(3):169–197. doi: 10.2165/00003495-197815030-00001. [DOI] [PubMed] [Google Scholar]
  14. Skovsgaard T. Mechanisms of resistance to daunorubicin in Ehrlich ascites tumor cells. Cancer Res. 1978 Jun;38(6):1785–1791. [PubMed] [Google Scholar]
  15. Tsuruo T., Iida H., Tsukagoshi S., Sakurai Y. Increased accumulation of vincristine and adriamycin in drug-resistant P388 tumor cells following incubation with calcium antagonists and calmodulin inhibitors. Cancer Res. 1982 Nov;42(11):4730–4733. [PubMed] [Google Scholar]

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