Suputtamongkol Y, Newton P N, Angus B, Teja-Isavadharm P, Keeratithakul D, Rasameesoraj M, Pukrittayakamee S, White N J
Department of Medicine, Siriraj Hospital, Bangkok, Thailand.
Br J Clin Pharmacol. 2001 Dec;52(6):655-61. doi: 10.1046/j.1365-2125.2001.01458.x.
Artesunate and artemether are the two most widely used artemisinin derivatives in the treatment of uncomplicated Plasmodium falciparum malaria, but there is little information on their comparative pharmacokinetics. The aim of this study was to examine the relative oral antimalarial bioavailability and pharmacokinetics of the two derivatives.
The pharmacokinetic properties of oral artesunate and artemether (4 mg kg(-1)) were compared in a randomized cross-over study of 14 adult patients in western Thailand with acute uncomplicated Plasmodium falciparum malaria. Antimalarial activity was compared using a previously validated, sensitive bioassay.
Despite a 29% lower molar dose, oral artesunate administration resulted in significantly larger mean area under the plasma antimalarial activity time curve and median maximum plasma antimalarial activity than after oral artemether (P <or= 0.02). The mean (95% CI) oral antimalarial bioavailability of artemether, relative to oral artesunate, corrected for molar dose was 58 (40-76)%. The mean (95% CI) relative antimalarial bioavailability of artemether was lower on the first day of treatment, 31 (17-100)%, compared to the second day, 72 (44-118)% (P = 0.018). In vivo parasite clearance and time above the in vitro IC90 were similar for the two drugs, despite considerable differences in Cmax and AUC.
The oral antimalarial bioavailability following artemether was significantly lower than that after artesunate. Artemether oral antimalarial bioavailability is reduced in acute malaria.
青蒿琥酯和蒿甲醚是治疗非复杂性恶性疟原虫疟疾最广泛使用的两种青蒿素衍生物，但关于它们的比较药代动力学信息很少。本研究的目的是研究这两种衍生物的相对口服抗疟生物利用度和药代动力学。
在泰国西部14例患有急性非复杂性恶性疟原虫疟疾的成年患者中进行随机交叉研究，比较口服青蒿琥酯和蒿甲醚（4mg/kg）的药代动力学特性。使用先前验证的敏感生物测定法比较抗疟活性。
尽管摩尔剂量低29%，但口服青蒿琥酯后血浆抗疟活性时间曲线下的平均面积和血浆抗疟活性最大值中位数均显著大于口服蒿甲醚后（P≤0.02）。相对于口服青蒿琥酯，经摩尔剂量校正后，蒿甲醚的平均（95%CI）口服抗疟生物利用度为58（40 - 76）%。与第二天的72（44 - 118）%相比，蒿甲醚在治疗第一天的平均（95%CI）相对抗疟生物利用度较低，为31（17 - 100）%（P = 0.018）。尽管两种药物的Cmax和AUC存在显著差异，但体内寄生虫清除率和高于体外IC90的时间相似。
蒿甲醚后的口服抗疟生物利用度显著低于青蒿琥酯。急性疟疾时蒿甲醚的口服抗疟生物利用度降低。
