Abstract
The potential for the modification of the pharmacokinetics of doxorubicin (DOX) concurrently administered with high-dose verapamil (VER) has been investigated in 17 patients with advanced neoplasms refractory to drugs belonging to the multidrug resistance spectrum. Steady-state concentration of DOX, systemic clearance and urinary excretion were analysed. No significant difference was found between the kinetic parameters estimated for DOX at different levels of VER and those reported for doxorubicin as single agent. It can be concluded that VER does not appear to modify DOX kinetics.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Boiocchi M., Toffoli G. Mechanism of multidrug resistance in human tumour cell lines and complete reversion of cellular resistance. Eur J Cancer. 1992;28A(6-7):1099–1105. doi: 10.1016/0959-8049(92)90465-e. [DOI] [PubMed] [Google Scholar]
- Booser D. J., Hortobagyi G. N. Anthracycline antibiotics in cancer therapy. Focus on drug resistance. Drugs. 1994 Feb;47(2):223–258. doi: 10.2165/00003495-199447020-00002. [DOI] [PubMed] [Google Scholar]
- Eksborg S., Strandler H. S., Edsmyr F., Näslund I., Tahvanainen P. Pharmacokinetic study of i.v. infusions of adriamycin. Eur J Clin Pharmacol. 1985;28(2):205–212. doi: 10.1007/BF00609693. [DOI] [PubMed] [Google Scholar]
- Kerr D. J., Graham J., Cummings J., Morrison J. G., Thompson G. G., Brodie M. J., Kaye S. B. The effect of verapamil on the pharmacokinetics of adriamycin. Cancer Chemother Pharmacol. 1986;18(3):239–242. doi: 10.1007/BF00273394. [DOI] [PubMed] [Google Scholar]
- Lai G. M., Chen Y. N., Mickley L. A., Fojo A. T., Bates S. E. P-glycoprotein expression and schedule dependence of adriamycin cytotoxicity in human colon carcinoma cell lines. Int J Cancer. 1991 Nov 11;49(5):696–703. doi: 10.1002/ijc.2910490512. [DOI] [PubMed] [Google Scholar]
- Lum B. L., Kaubisch S., Yahanda A. M., Adler K. M., Jew L., Ehsan M. N., Brophy N. A., Halsey J., Gosland M. P., Sikic B. I. Alteration of etoposide pharmacokinetics and pharmacodynamics by cyclosporine in a phase I trial to modulate multidrug resistance. J Clin Oncol. 1992 Oct;10(10):1635–1642. doi: 10.1200/JCO.1992.10.10.1635. [DOI] [PubMed] [Google Scholar]
- Salama Z. B., Dilger C., Czogalla W., Otto R., Jaeger H. Quantitative determination of verapamil and metabolites in human serum by high-performance liquid chromatography and its application to biopharmaceutic investigations. Arzneimittelforschung. 1989 Feb;39(2):210–215. [PubMed] [Google Scholar]
- Speth P. A., van Hoesel Q. G., Haanen C. Clinical pharmacokinetics of doxorubicin. Clin Pharmacokinet. 1988 Jul;15(1):15–31. doi: 10.2165/00003088-198815010-00002. [DOI] [PubMed] [Google Scholar]
- Toffoli G., Tumiotto L., Gigante M., Dall'Arche M. G., Perin T., Boiocchi M. Increased chemosensitivity to doxorubicin of intrinsically multidrug-resistant human colon carcinoma cells by prolonged exposure to verapamil. Eur J Cancer. 1993;29A(12):1776–1778. doi: 10.1016/0959-8049(93)90123-w. [DOI] [PubMed] [Google Scholar]
- Tsuruo T., Iida H., Nojiri M., Tsukagoshi S., Sakurai Y. Circumvention of vincristine and Adriamycin resistance in vitro and in vivo by calcium influx blockers. Cancer Res. 1983 Jun;43(6):2905–2910. [PubMed] [Google Scholar]
- Zanette L., Zucchetti M., Freshi A., Erranti D., Tirelli U., D'Incalci M. Pharmacokinetics of 4-demethoxydaunorubicin in cancer patients. Cancer Chemother Pharmacol. 1990;25(6):445–448. doi: 10.1007/BF00686057. [DOI] [PubMed] [Google Scholar]