Modulation of doxorubicin efficacy in P388 leukemia following co-administration of verapamil in mini-osmotic pumps.

Autor: Slate DL; Institute of Biochemistry and Cell Biology, Syntex Discovery Research, Palo Alto, CA 94304., Fraser-Smith EB, Rosete JD, Freitas VR, Kim YN, Casey SM
Jazyk: angličtina
Zdroj: In vivo (Athens, Greece) [In Vivo] 1993 Nov-Dec; Vol. 7 (6A), pp. 519-23.
Abstrakt: Co-administration of doxorubicin and verapamil in Alzet mini-osmotic pumps increased the survival of B6D2F1 mice bearing the multidrug-resistant P388/ADR leukemia. A range of doxorubicin and verapamil combinations was studied to define dose-dependent efficacy and toxicity. High doses of doxorubicin (10 mg/kg/day) and verapamil (150 mg/kg/day) could be administered alone without any effect on survival. However, combining high doses of these two agents resulted in host toxicity. Doxorubicin doses of 1 to 10 mg/kg/day in combination with verapamil at 25-100 mg/kg/day were found to improve survival compared with either agent alone. Combination therapy also improved the survival of mice bearing the drug-sensitive P388/0 leukemia when compared to anthracycline treatment alone. The efficacy of the mini-osmotic pump delivery protocol was compared with other regimens delivering the same total cumulative dose of doxorubicin via repeated i.p. injections.
Databáze: MEDLINE