Stewart D J, Green R M, Mikhael N Z, Montpetit V, Thibault M, Maroun J A
Cancer Treat Rep. 1986 Nov;70(11):1255-61.
A sensitive high-performance liquid chromatography method was used to measure mitoxantrone in autopsy tissue samples of 11 patients who had received the drug iv 10-272 days antemortem. Mitoxantrone was readily detectable in tissues from all patients. Tissue concentrations were proportional to lifetime cumulative dose of mitoxantrone, and decreased very slowly with time. The thyroid and the liver had the highest mitoxantrone concentrations, followed by the heart. These high cardiac concentrations of mitoxantrone could be partially responsible for the occasional case of cardiotoxicity seen with mitoxantrone. The brain had the lowest mitoxantrone concentrations. Organ mitoxantrone concentrations did not conform to a flow-limited model. Tumor mitoxantrone concentrations varied quite markedly from one site to another in the same patient. Tumors generally had lower mitoxantrone concentrations than did surrounding normal tissues. Mitoxantrone concentrations were consistently highest in intrahepatic tumors and lowest in intracerebral tumors. It is unclear whether the low concentrations in brain tumors were due to a partially intact blood-brain barrier or to the fact that most brain tumors had been irradiated prior to mitoxantrone administration. Further studies are warranted to more fully explore the relationship between human tissue mitoxantrone concentrations and efficacy and toxicity.
采用灵敏的高效液相色谱法，对11例生前10 - 272天静脉注射米托蒽醌的患者尸检组织样本中的米托蒽醌进行测定。在所有患者的组织中均易于检测到米托蒽醌。组织浓度与米托蒽醌的终生累积剂量成正比，且随时间下降非常缓慢。甲状腺和肝脏中的米托蒽醌浓度最高，其次是心脏。米托蒽醌在心脏中的高浓度可能是米托蒽醌偶尔出现心脏毒性病例的部分原因。大脑中的米托蒽醌浓度最低。器官中的米托蒽醌浓度不符合流量限制模型。同一患者不同部位肿瘤的米托蒽醌浓度差异相当明显。肿瘤中的米托蒽醌浓度通常低于周围正常组织。肝内肿瘤中的米托蒽醌浓度始终最高，脑内肿瘤中的浓度最低。尚不清楚脑肿瘤中低浓度是由于血脑屏障部分完整，还是由于大多数脑肿瘤在给予米托蒽醌之前已接受过放疗。有必要进行进一步研究，以更全面地探讨人体组织米托蒽醌浓度与疗效及毒性之间的关系。
