Alterations in the C-9 side chain of the anthracycline antibiotics, adriamycin and daunorubicin, have a profound effect on antibiotic uptake and accumulation by cultured L1210 cells. The degree of inhibition of DNA and RNA biosynthesis in the L1210 cells is directly related to the cellular uptake and accumulation of the drug analogues. Polar drug metabolites, daunorubicinol and adriamycinol, retain inhibitory activity against nucleic acid metabolism but have a decreased membrane binding and permeability. Cellular uptake and accumulation of the C-9 analogues are inversely related to drug polarity. We propose that the polarity of the anthracycline analogues contributes heavily to the differences in therapeutic index and in vivo activity through fundamental effects on membrane permeability, metabolism, and macromolecular binding.

Survival after severe hyponatremia (serum sodium 125 mEq/l) and hypochloremia (serum chloride 78 mEq/l) is described in an adult with acute leukemia who received toxic doses of vincristine. Transient confusion and prostration accompanied the electrolyte abnormalities. Laboratory evidence of CNS leukemia was not present. The patient with supportive care improved rapidly within two days as the electrolytes gradually returned toward normal; the electrolytes became entirely normal on the fifth day. Stringent sodium chloride replacement was not required to correct the hyponatremia and hypochloremia. Although rare, vincristine-induced hyponatremia and hypochloremia constitute a serious complication that warrants prompt recognition and supportive medical care.

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