Multiple dose pharmacokinetics of oral artemisinin and comparison of its efficacy with that of oral artesunate in falciparum malaria patients
Multiple dose pharmacokinetics of oral artemisinin and comparison of its efficacy with that of oral artesunate in falciparum malaria patients
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DOI：
10.1016/s0035-9203(96)90480-0
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发表时间：
1996-01-01
影响因子：
2.2
通讯作者：
Bjorkman, A
中科院分区：
文献类型：
--
作者：
Alin, MH;Ashton, M;Bjorkman, A
该研究比较了口服青蒿素和口服青蒿琥酯的临床疗效和安全性，以及恶性疟消退期间和消退后青蒿素的药代动力学。 40 名患有症状性恶性疟疾的成年人被随机分配接受口服青蒿素治疗（第 1 天单剂量 500 mg，随后每天两次 250 mg，持续 4 天，然后第 6 天再接受单剂量 500 mg）或口服青蒿琥酯治疗（第 1 天单剂量 100 mg，随后每天两次 50 mg，持续 5 天）。患者在坦桑尼亚基巴哈指定地区医院接受治疗。患者每周复诊一次，持续 3 周。口服青蒿琥酯后的寄生虫清除时间（PCT）（26.4+/-3.6小时）比青蒿素口服后（31+/-3.6小时）短（P=0.002）。口服青蒿琥酯后的退烧时间（FST）（18.9+/-4.0 h）也比青蒿素口服后（21.8+/-4.6 h）短（P=0.04）。完成青蒿琥酯和青蒿素治疗后，分别有 4 名（20%）和 7 名（35%）患者检测到寄生虫。这些患者在随访的第 3 或第 4 周再次出现寄生虫血症。在服药前以及第 6 天和第 14 天再次进行的标准血液学、血液生化和尿液分析均正常。研究期间未观察到临床异常。第 1 天和第 6 天给药后 8 小时，通过柱后衍生化和紫外光检测的高效液相色谱法测定青蒿素血浆浓度。青蒿素吸收迅速，约 3 小时达到最大血浆浓度 (C-max)。青蒿素血浆浓度-时间曲线下面积 (AUG) 和 C-max 值在第 1 天首次给药后比第 6 天高约 6 倍。青蒿素血浆浓度的下降表明由于明显的自诱导而导致代谢能力增加。
The study compared the clinical efficacy and safety of oral artemisinin and oral artesunate as well as artemisinin pharmacokinetics during and after resolution of falciparum malaria. Forty adults with symptomatic falciparum malaria were allocated at random to treatment with either oral artemisinin (500 mg single dose on day 1 followed by 250 mg twice daily for 4 d and then another 500 mg single dose on day 6) or with oral artesunate (100 mg single dose on day 1 followed by 50 mg twice daily for 5 d). Patients were admitted to hospital at the Kibaha Designated District Hospital, Kibaha, Tanzania for the duration of treatment. The patients were seen once weekly for 3 more weeks. The time to parasite clearance (PCT) after oral artesunate (26.4+/-3.6 h) was shorter (P=0.002) than after artemisinin (31+/-3.6 h). The fever subsidence time (FST) after oral artesunate (18.9+/-4.0 h) was also shorter (P=0.04) than after artemisinin (21.8+/-4.6 h). Parasites were detected in 4 (20%) and 7 (35%) patients after completing treatment with artesunate and artemisinin respectively. In these patients the parasitaemia reappeared at the 3rd or 4th week of follow-up. Standard haematology, blood biochemistry and urinanalysis, performed before drug intake and again on days 6 and 14, were normal. No clinical abnormality was observed during the study period. Artemisinin plasma concentrations, determined by high performance liquid chromatography with post-column derivatization and detection by ultraviolet light, were followed up to 8 h after drug administration on days 1 and 6. Artemisinin absorption was rapid, the maximum plasma concentrations (C-max) being attained at about 3 h. Artemisinin areas under the plasma concentration-time curve (AUG) and the C-max values were about 6 times higher after the first dose on day 1 than on day 6. This decrease in artemisinin plasma concentration is suggestive of an increase in metabolic capacity due to pronounced autoinduction.