Dorr R T, Peng Y M, Alberts D S
Invest New Drugs. 1984;2(4):351-7. doi: 10.1007/BF00171585.
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).
分别通过腹腔注射（IP）和皮内注射（ID）给药，研究了双胺苯吖啶在小鼠体内的溶解度和皮肤毒性。5%葡萄糖溶液中1mg/ml的双胺苯吖啶在小鼠腹膜内极易沉淀。双胺苯吖啶与各种亲脂性溶剂混合，在37℃时，并未减少其在小鼠体内或人血浆体外的沉淀。使用高效液相色谱法（HPLC）进行的药物稳定性研究表明，在碱性pH条件下，双胺苯吖啶的稳定性显著降低。BALB/c小鼠皮内注射双胺苯吖啶后，皮肤毒性表现为溃疡，持续长达四个月。向双胺苯吖啶外渗部位注射稀释的碳酸氢钠可持续减轻皮肤毒性。三例用碳酸氢钠治疗的临床外渗病例均未出现双胺苯吖啶溃疡。无效的局部解毒剂包括色甘酸钠、N-乙酰半胱氨酸、氢化可的松和热敷（似乎会增加毒性）。
