Bisantrene solubility and skin toxicity studies: efficacy of sodium bicarbonate as a local ulceration antidote.
Bisantrene solubility and skin toxicity were studied in mice given intraperitoneal (IP) and intradermal (ID) drug respectively. Bisantrene (1 mg/ml) in 5% dextrose readily precipitated in the mouse peritoneum. The admixture of bisantrene into various lipophilic solvents did not reduce drug precipitation in vivo in the mouse or in vitro in human plasma at 37 degrees C. Drug stability studies using high performance liquid chromatography (HPLC) showed markedly reduced bisantrene stability at alkaline pH. Bisantrene skin toxicity in BALB/c mice was characterized by ulceration which persisted for up to four months after ID injection. Skin toxicity was consistently reduced by dilute sodium bicarbonate injection into the bisantrene extravasation site. Three clinical extravasation cases treated with sodium bicarbonate showed no bisantrene ulceration. Ineffective local antidotes included sodium cromolyn, N-acetylcysteine, hydrocortisone, and heat (which appeared to increase toxicity).
D000368:Aged; D000818:Animals; D000873:Anthracenes / Q000009:adverse effects / Q000627:therapeutic use / Q000633:toxicity; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use / Q000633:toxicity*; D001639:Bicarbonates / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002986:Clinical Trials as Topic; D004344:Drug Incompatibility; D004355:Drug Stability; D004890:Erythema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D012883:Skin Ulcer / Q000188:drug therapy*; D017693:Sodium Bicarbonate; D012995:Solubility
D000873:Anthracenes; D000903:Antibiotics, Antineoplastic; D001639:Bicarbonates; C031404:bisantrene; D017693:Sodium Bicarbonate