Verdier F, Pussard E, Blayo M C
Med Trop (Mars). 1986 Oct-Dec;46(4):329-43.
The development of new sensitive and specific assays (HPLC) have enabled the pharmacokinetics of antimalarial drugs to be studied. Parameters such as half-life distribution volume, clearance and bioavailability, are defined. In healthy subjects, quinine is rapidly eliminated (t1/2 beta: 6-12 h). Hepatic biotransformation accounts for approximately 80% of its total clearance. In malaria, the pharmacokinetic properties of quinine (decrease in the apparent volume of distribution, prolongation of the t1/2 beta, reduction in systemic clearance), are altered in proportion to the severity of infection. Red cell concentrations and plasma binding are increased. Parenteral quinine should be given by slow intravenous infusion and a loading dose is recommended in severe infections. Chloroquine (t1/2 beta: 6-50 days) and mefloquine (t1/2 beta: 6-33 days) have extensive tissue distribution and prolonged activity after a single dose. Both drugs are concentrated in erythrocytes and are bound considerably to plasma proteins. Amodiaquine is not found in the blood after oral administration. Hepatic biotransformation accounts for almost all orally administered drug. Its antiplasmodial activity is thus almost entirely due to monodesethylamodiaquine, the main metabolite. In healthy subjects, the t1/2 beta of this metabolite is 9 to 18 days in plasma. Amodiaquine is concentrated in erythrocytes. The protein binding of this drug has not been studied to date. For prophylaxis, it has been suggested that the dosage of 10 mg/kg/wk should be spread over the week (3.5 mg/kg every other day, or 1.5 every day). Halofantrine has an elimination half-life of between 1.3 and 6.6 days. This drug has been suggested as a single-dose treatment. No pharmacokinetic studies of qinghaosu have been reported in humans. In rabbits, the elimination half-life in plasma was found to be 40 min. Although rapidly eliminated, this drug appears to be highly effective. More information is required on the pharmacokinetics of these drugs in malaria, during pregnancy, in children and in renal and hepatic failure.
新型灵敏且特异的检测方法（高效液相色谱法）的发展，使得抗疟药物的药代动力学得以研究。诸如半衰期、分布容积、清除率和生物利用度等参数得以确定。在健康受试者中，奎宁迅速被清除（β半衰期：6 - 12小时）。肝脏生物转化约占其总清除率的80%。在疟疾患者中，奎宁的药代动力学特性（分布容积减小、β半衰期延长、全身清除率降低）会随着感染严重程度而改变。红细胞浓度和血浆结合率增加。静脉注射奎宁应缓慢输注，严重感染时建议给予负荷剂量。氯喹（β半衰期：6 - 50天）和甲氟喹（β半衰期：6 - 33天）单次给药后具有广泛的组织分布和持久的活性。这两种药物都集中在红细胞中，并与血浆蛋白大量结合。口服氨苯喹后血液中未检测到该药物。肝脏生物转化几乎占口服给药药物的全部。因此，其抗疟活性几乎完全归因于主要代谢产物单脱乙基氨苯喹。在健康受试者中，该代谢产物在血浆中的β半衰期为9至18天。氨苯喹集中在红细胞中。该药物的蛋白结合情况至今尚未研究。对于预防，有人建议每周10 mg/kg的剂量应在一周内分服（每隔一天3.5 mg/kg，或每天1.5 mg/kg）。卤泛群的消除半衰期在1.3至6.6天之间。该药物被建议作为单剂量治疗药物。尚未有关于青蒿素在人体药代动力学的研究报道。在兔子中，发现其血浆消除半衰期为40分钟。尽管清除迅速，但该药物似乎非常有效。关于这些药物在疟疾患者、孕妇、儿童以及肾衰竭和肝衰竭患者中的药代动力学，还需要更多信息。
