Tan H W, Ch'ng S L
Department of Medicine, University Hospital, University of Malaya, Kuala Lumpur, Malaysia.
Singapore Med J. 1991 Jun;32(3):189-90.
We report a previously undocumented drug interaction between cyclosporine A and quinine. A 39 year old Asian with a recent renal transplant was diagnosed to have a mild cerebral falciparum malaria. He was treated with seven days of oral quinine (600 mg, 8 hourly), followed by a stat dose of pyrimethamine (75 mg)--sulfadoxime (1200mg) because of a strong suspicion of chloroquine resistant falciparum malaria. Using a polyclonal radioimmunoassay method, we measured morning trough cyclosporine A level before, during and after the quinine treatment. Results showed a gradual decrease in the cyclosporine A level from a baseline value of 328 ng/ml to 107 ng/ml after seven days of oral quinine with a subsequent rise to pre-treatment level after discontinuation of quinine. There was no significant change in the dose of cyclosporine A administered during the period of quinine treatment (4.05 to 3.83 mg/kg body weight). Biochemical liver function tests, serum creatinine and hematological parameters were also essentially unchanged during this period. In vitro study showed no significant methodological interference in the cyclosporine assay by quinine dihydrochloride. These findings suggest an in vivo drug interaction between cyclosporine A and quinine. The mechanism of this interaction is not clear. Further studies are required to confirm the significance of this observation. Quinine and its stereoisomer, quinidine should be used with caution until further information is available.
我们报告了环孢素A与奎宁之间一种此前未被记录的药物相互作用。一名39岁近期接受肾移植的亚洲人被诊断患有轻度脑型恶性疟。因其高度怀疑为氯喹耐药的恶性疟,先接受了7天的口服奎宁治疗(600毫克,每8小时一次),随后即刻给予了乙胺嘧啶(75毫克)-磺胺多辛(1200毫克)一剂。我们采用多克隆放射免疫测定法,在奎宁治疗前、治疗期间和治疗后测量了环孢素A的晨间谷浓度。结果显示,口服奎宁7天后,环孢素A水平从基线值328纳克/毫升逐渐降至107纳克/毫升,停用奎宁后随后又回升至治疗前水平。在奎宁治疗期间,所给予的环孢素A剂量(4.05至3.83毫克/千克体重)没有显著变化。在此期间,生化肝功能检查、血清肌酐和血液学参数也基本未变。体外研究表明,盐酸奎宁对环孢素测定没有显著的方法学干扰。这些发现提示环孢素A与奎宁之间存在体内药物相互作用。这种相互作用的机制尚不清楚。需要进一步研究以证实这一观察结果的意义。在获得更多信息之前,应谨慎使用奎宁及其立体异构体奎尼丁。