Solary E, Velay I, Chauffert B, Caillot D, Bidan J M, Dumas M, Casasnovas O, Guy H
Hématologie Clinique, Centre Hospitalier Universitaire Le Bocage, Dijon, France.
Nouv Rev Fr Hematol (1978). 1990;32(5):361-3.
Reversal of multidrug resistance (MDR) has been obtained in vitro by a variety of agents but clinical use of these resistance modifiers is hampered by their own toxicity. Quinine, the natural isomer of quinidine, is demonstrated to circumvent doxorubicin (DXR) resistance of an MDR human leukemic cell-line, K562/DXR. In culture medium, quinine (5 mu/ml or more) significantly increases cytotoxicity and accumulation of DXR in the resistant cells but not in the parental sensitive cells. When quinine is administered by continuous intravenous infusion in the doses conventionally used in chloroquino-resistant malaria (30 mg/kg/d), serum levels reach 8-11 micrograms/ml without prohibitive toxicity. Sera from quinine-treated patients enhance DXR uptake in K562/DXR cells in dose-dependent fashion. The conditions for the safe use of quinine as an MDR modifier in the treatment of refractory human hemopoietic malignancies are defined.
多种药物已在体外实现了对多药耐药性（MDR）的逆转，但这些耐药性修饰剂因其自身毒性而阻碍了在临床上的应用。奎宁是奎尼丁的天然异构体，已证明其可克服多药耐药人类白血病细胞系K562/DXR对阿霉素（DXR）的耐药性。在培养基中，奎宁（5μ/ml或更高）可显著增加耐药细胞中DXR的细胞毒性和蓄积，但对亲本敏感细胞则无此作用。当以耐氯喹疟疾常规使用的剂量（30mg/kg/d）通过持续静脉输注给予奎宁时，血清水平可达8-11μg/ml，且无严重毒性。奎宁治疗患者的血清以剂量依赖方式增强K562/DXR细胞对DXR的摄取。本文确定了在难治性人类造血系统恶性肿瘤治疗中安全使用奎宁作为MDR修饰剂的条件。
