Abstract
The degree of cardiotoxicity of SM-5887 compared with that of doxorubicin was investigated in rabbits.
Two experimental groups were administered high and low doses of SM-5887, respectively. One group was administered doxorubicin and another group was administered the vehicle only were prepared as positive and negative controls, respectively. Drugs were intravenously administered 3 times a week for 8 weeks.
At terminus, electrocardiograms were recorded under anesthesia. The blood was collected for haematology and blood biochemistry analyses. Myocardial tissue damage was evaluated using light and electron microscopy.
In the electrocardiogram study, prolongation of QTc interval and ST-T change were observed in rabbits administered SM-5887 and doxorubicin.
Morphological studies showed that myocardial tissue damage in animals administered SM-5887 was comparable to that in the negative controls, and less than that observed in the positive controls.
The general toxicological investigations uniformly indicated lower toxicity in the SM-5887 group than in the doxorubicin group at equivalent dosages.
In total, considering the results of antitumor efficacy studies comparing SM-5887 with doxorubicin, these results indicate that the cardiotoxicity of SM-5887 is very slight, and that the general toxicity of SM-5887 is lower than that of doxorubicin.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Young RC, Ozols RF, Myers CE: The anthracycline antineoplastic drugs. N Engl J Med 305: 139–153, 1981.
Suzuki T, Kanda H, Kawai Y, Tominaga K, Murata K: Cardiotoxicity of anthracycline antineoplastic drugs-clinicopathological and experimental studies. Jpn Circ J 43: 1000–1008, 1978.
Ishizumi K, Ohashi N, Tanno N: Stereoscopic total synthesis of 9 Aminoanthracycline: (+)-9-amino-9-deoxydaunomycin and related compounds. J Org Chem 52: 4477–4485, 1987.
Morisada S, Yanagi Y, Noguchi T, Kashiwagi Y, Fukui M: Antitumor activities of a novel 9-aminoanthracycline (SM-5887) against mouse experimental tumors and human tumor xenografts. Jpn J Cancer Res 80: 69–76, 1989.
Morisada S, Yanagi Y, Noguchi T, Kashiwagi Y, Fukui M: Toxicological aspects of a novel 9-aminoanthracycline, SM-5887. Jpn J Cancer Res 80: 77–82, 1989.
Bertazzoli C, Bellini O, Magrini U, Tosana MG: Quantitative experimental evaluation of adriamycin cardiotoxicity in the mouse. Cancer Treat Rep 63: 1877–1883, 1979.
Ferrans VJ: Overview of cardiac pathology in relation to anthracycline cardiotoxicity. Cancer Treat Rep 62: 955–961, 1978.
Suzuki T, Yamamoto H, Iwasaki T, Okamoto S, Iizuka T, Kanda H, Murata K: A comparative study of 4′-epidoxorubicin and doxorubicin cardiotoxicities. Jpn J Cancer Chemother 11: 2170–2176, 1984.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Suzuki, T., Minamide, S., Iwasaki, T. et al. Cardiotoxicity of a new anthracycline derivative (SM-5887) following intravenous administration to rabbits: Comparative study with doxorubicin. Invest New Drugs 15, 219–225 (1997). https://doi.org/10.1023/A:1005862730941
Issue Date:
DOI: https://doi.org/10.1023/A:1005862730941