Pharmacokinetic and Pharmacodynamic Profiles of Rapid-Acting Artemisinins in the Antimalarial Therapy
Pharmacokinetic and Pharmacodynamic Profiles of Rapid-Acting Artemisinins in the Antimalarial Therapy
复制标题
DOI：
10.2174/157488507781695649
复制
发表时间：
2007-01-01
影响因子：
0.6
通讯作者：
Milhous, Wilbur K.
中科院分区：
文献类型：
--
作者：
Li, Qigui;Weina, Peter J.;Milhous, Wilbur K.
青蒿素及其衍生物被发现是非常有效的抗疟药物，它们将联合收割机有效、快速的抗疟活性与广泛的治疗指数结合起来，并且不存在临床上重要的耐药性。青蒿素作为一种单一疗法在治疗疟疾方面效果不佳。然而，通过使用口服青蒿素综合疗法和静脉注射青蒿琥酯与作用较慢的抗疟药物序贯给药，正在克服这一不足。药代动力学和药效学（PK/PD）评价表明，青蒿素的快速疗效主要是由于药物峰浓度（C-max），其他药代动力学参数，如药物暴露水平（AUC）和药物暴露时间（半衰期）往往意义不大。评价还表明，与其他四种青蒿素药物相比，AS在口服或静脉给药后的PK/PD成就方面具有上级优势。最近，在一项大型研究中，使用静脉注射AS与标准治疗奎宁注射剂相比，死亡率降低（34.7%）。疗效快、死亡率低表明，目前青蒿素类药物在以青蒿素为基础的联合疗法治疗无并发症疟疾和AS注射液序贯疗法治疗重症和并发症疟疾方面具有明显优势。
Artemisinin and its derivatives were discovered to be highly effective antimalarial drugs, which combine potent, rapid antimalarial activity with a wide therapeutic index and an absence of clinically important resistance. Artemisinins as a group are poorly efficacious at curing malaria as monotherapy. However, this shortfall is being overcome by using oral artemisinin-based combination therapy (ACT) and intravenous artesunate (AS) in sequential administration with slower acting antimalarial drugs. Pharmacokinetic and pharmacodynamic (PK/PD) evaluations demonstrate that the rapid efficacy of artemisinins is principally due to the drug peak concentration (C-max), and other pharmacokinetic parameters, such as drug exposure level (AUC) and drug exposure time (half-life) tend to be of minor significance. The evaluation also demonstrated that AS is a superior in PK/PD achievements either following oral or intravenous administration when compared to other four artemisinin drugs. Most recently, a decrease in mortality (34.7%) has been demonstrated in a large study using intravenous AS, as opposed to the standard of care quinine injection. The fast efficacy and less mortality show that current artemisinins have great advantage over other antimalarials in ACTs for uncomplicated malaria and in sequential therapy of AS injection for severe and complicated malaria.