Phillips R E, Warrell D A, White N J, Looareesuwan S, Karbwang J
N Engl J Med. 1985 May 16;312(20):1273-8. doi: 10.1056/NEJM198505163122001.
Quinidine has proved more effective than quinine against chloroquine-resistant Plasmodium falciparum both in vitro and in patients with uncomplicated disease. To examine the effectiveness and pharmacokinetics of quinidine for this use, we treated 14 patients who had severe falciparum malaria with intravenous quinidine gluconate; a loading dose of 15 mg of the base per kilogram of body weight was followed by 7.5 mg per kilogram every eight hours. Two of the five patients with cerebral malaria died, but parasitemia was eliminated in the 12 survivors. Two patients had recurrent parasitemia on Days 25 and 28. Times required for parasite clearance and elimination of fever (49.4 +/- 17.8 and 69.5 +/- 18.7 hours, respectively) were comparable to those in earlier studies with a loading dose of quinine. Quinidine appears to have a larger volume of distribution than quinine. The elimination half-life was 12.8 hours, the volume of distribution was 1.68 liters per kilogram, total clearance was 1.75 ml per kilogram per minute, and urinary clearance was 0.62 ml per kilogram per minute. Electrocardiographic changes were common but there were no dysrhythmias. In two patients, blood pressure fell during the initial infusion of quinidine. Quinidine gluconate is more widely available than quinine in many countries, and our findings show that it is effective in severe falciparum malaria.
在体外实验以及针对非复杂性疾病患者的治疗中，奎尼丁已被证明在对抗氯喹耐药的恶性疟原虫方面比奎宁更有效。为了研究奎尼丁用于此用途的有效性和药代动力学，我们用静脉注射葡萄糖酸奎尼丁治疗了14例严重恶性疟疾病例；先给予每千克体重15毫克碱基的负荷剂量，随后每八小时给予每千克体重7.5毫克。五例脑型疟患者中有两例死亡，但12名幸存者的疟原虫血症被清除。两名患者在第25天和第28天出现疟原虫血症复发。疟原虫清除和退热所需时间（分别为49.4±17.8小时和69.5±18.7小时）与早期使用奎宁负荷剂量的研究结果相当。奎尼丁的分布容积似乎比奎宁大。消除半衰期为12.8小时，分布容积为每千克体重1.68升，总清除率为每分钟每千克体重1.75毫升，尿清除率为每分钟每千克体重0.62毫升。心电图改变很常见，但未出现心律失常。两名患者在最初输注奎尼丁时血压下降。在许多国家，葡萄糖酸奎尼丁比奎宁更容易获得，我们的研究结果表明它对严重恶性疟疾有效。
