STUDY OF JADOMYCIN PHARMACOKINETICS AND ANTI-BREAST CANCER ACTIVITY IN BALB/C MICE

Abstract

Breast cancer is the most common form of cancer in Canadian women. Despite numerous therapeutic options, multidrug resistance (MDR) remains an obstacle to successful therapy. Jadomycins are natural products derived from the soil bacteria Streptomyces venezuelae ISP5230 and maintain cytotoxicity in multidrug resistant human breast cancer cell lines. The objectives were to determine the single dose pharmacokinetics and safety of jadomycins and their effects on 4T1 breast primary tumors and lung metastasis in mice. In the pharmacokinetic studies, intraperitoneal-administered jadomycins B, S, and F were rapidly absorbed, achieved serum concentration in the predicted therapeutic range and had a biphasic distribution and elimination profile. In tumor studies jadomycin B partially reduced tumor volumes and lung metastasis. In conclusion, jadomycins are safe to administer chronically to mice at doses up to 13.8 mg/kg twice daily. The partial anti-tumor and anti-metastatic effects of jadomycin B were encouraging results and require further study.