科研之友
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摘要
BackgroundThe efficacy and biosafety of a previously established tolerable dosage of doxorubicin have not been established in horses. %26lt;br%26gt;ObjectivesTo provide preliminary evidence of the efficacy of doxorubicin in tumor-bearing horses, explore drug pharmacokinetics profile, and estimate period of risk of exposure to drug residues. %26lt;br%26gt;AnimalsTwelve horses with 37 tumors. %26lt;br%26gt;ProceduresTreatment protocol included 6 treatments at 3-week intervals. Eight horses were uniformly treated at a dosage of 70mg/m(2) and 4 horses received 4 of 6 treatment cycles at 70mg/m(2). Clinical signs, tumor responses, and toxicoses were evaluated. Drug residue concentrations were quantitated in 3 horses receiving of 65, 70, and 75mg/m(2) by high-performance liquid chromatography with ultraviolet detection (plasma, feces) and liquid chromatography and tandem mass spectrometry (urine). %26lt;br%26gt;ResultsThirty tumors, including lymphomas, carcinomas, sarcoids, and melanoma, were evaluated for efficacy. The overall response rate was 47% (95% CI, 28-65%). Doxorubicin was not found to be effective against melanomas. Lymphomas and carcinomas were most responsive. Pooled serum Cmax and half-life of doxorubicin were 121.3ng/mL and 12.9hours, respectively. There were no detectable residues in fecal samples up to 3weeks after treatment and in plasma and urine after 2 and 3days, respectively. %26lt;br%26gt;Conclusion and Clinical RelevanceThis study provides preliminary evidence that single-agent doxorubicin at a dosage of 70mg/m(2) has a broad spectrum of activity. The risk of exposure to drug residues in plasma and feces was low. Direct contact with urine-contaminated wastes should be avoided for 2days after treatment.
- 出版日期2013-11
