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  • Title: Modulation of doxorubicin efficacy in P388 leukemia following co-administration of verapamil in mini-osmotic pumps.
    Author: Slate DL, Fraser-Smith EB, Rosete JD, Freitas VR, Kim YN, Casey SM.
    Journal: In Vivo; 1993; 7(6A):519-23. PubMed ID: 8193270.
    Abstract:
    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.
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