Metabolism and Pharmacokinetics Department, Ranbaxy Research Laboratories, Plot # 20, Sector-18, Udhyog Vihar Industrial Area, Gurgaon-122015, Haryana, India.
J Clin Pharmacol. 2011 Nov;51(11):1519-28. doi: 10.1177/0091270010385578. Epub 2010 Dec 8.
Arterolane (RBx 11160) maleate is a novel, rapidly acting synthetic trioxolane antimalarial compound being developed by Ranbaxy Research Laboratories (Haryana, India). It is presently under phase III in combination with piperaquine phosphate. The present work reports the relationship between pharmacokinetic (PK) parameter (AUC(0-8h) on day 0/day 6) and indices of pharmacodynamic (PD) response (50% parasite clearance [PC(50)], 90% parasite clearance [PC(90)], parasite clearance time [PCT], recrudescence) from a phase II, double-blind, multicenter, randomized, parallel-group, dose-ranging trial. Patients with acute uncomplicated P. falciparum malaria were randomized to 1 of 3 arterolane maleate (50, 100, and 200 mg) doses for 7 consecutive days. Plasma concentration data were available from 78, 76, and 75 patients receiving a 50-, 100-, and 200-mg dose, respectively. Based on PD modeling, its limitations and assumptions, minimum 150-mg dose arterolane maleate was recommended to optimize the probability of maximum therapeutic benefits for an adult. Doses higher than 100 mg are unlikely to reduce the probability of recrudescence. This study re-stresses the need of combining short and long-acting drugs to prevent resistance development and minimize recrudescence.
马来酸氨苯砜（RBx 11160）是 Ranbaxy 研究实验室（印度哈里亚纳邦）正在开发的一种新型、快速作用的合成三噁烷抗疟化合物。它目前正在与磷酸哌喹联合进行 III 期临床试验。本研究报告了药代动力学（PK）参数（第 0 天/第 6 天的 AUC（0-8h））与药效学（PD）反应指标（50%寄生虫清除率[PC（50）]、90%寄生虫清除率[PC（90）]、寄生虫清除时间[PCT]、复燃）之间的关系，这是一项 II 期、双盲、多中心、随机、平行组、剂量范围试验。患有急性无并发症恶性疟原虫疟疾的患者被随机分配至 3 种马来酸氨苯砜（50、100 和 200 mg）剂量组中，连续给药 7 天。分别有 78、76 和 75 名接受 50、100 和 200 mg 剂量的患者提供了血浆浓度数据。基于 PD 建模、其局限性和假设，建议使用最低 150 mg 剂量的马来酸氨苯砜，以优化最大治疗效果的可能性。剂量高于 100 mg 不太可能降低复燃的概率。这项研究再次强调了需要结合使用短效和长效药物来预防耐药性的发展并最小化复燃。
