Hassan Alin M, Ashton M, Kihamia C M, Mtey G J, Björkman A
Department of Pharmacy, Uppsala University, Sweden.
Trans R Soc Trop Med Hyg. 1996 Jan-Feb;90(1):61-5. doi: 10.1016/s0035-9203(96)90480-0.
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 urinalysis, 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 (Cmax) being attained at about 3 h. Artemisinin areas under the plasma concentration-time curve (AUC) and the Cmax 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.
该研究比较了口服青蒿素和口服青蒿琥酯的临床疗效与安全性，以及恶性疟治愈期间及治愈后的青蒿素药代动力学。40名有症状的恶性疟成年患者被随机分配接受口服青蒿素（第1天单次服用500毫克，随后4天每天两次服用250毫克，然后在第6天再单次服用500毫克）或口服青蒿琥酯（第1天单次服用100毫克，随后5天每天两次服用50毫克）治疗。患者在坦桑尼亚基巴哈指定地区医院住院接受治疗。之后3周每周对患者进行一次检查。口服青蒿琥酯后的寄生虫清除时间（PCT）（26.4±3.6小时）比口服青蒿素后（31±3.6小时）短（P = 0.002）。口服青蒿琥酯后的退热时间（FST）（18.9±4.0小时）也比口服青蒿素后（21.8±4.6小时）短（P = 0.04）。分别完成青蒿琥酯和青蒿素治疗后，有4名（20%）和7名（35%）患者检测到寄生虫。在这些患者中，寄生虫血症在随访的第3周或第4周再次出现。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。通过柱后衍生化高效液相色谱法并采用紫外光检测来测定青蒿素血浆浓度，在第1天和第6天给药后对其进行长达8小时的随访。青蒿素吸收迅速，大约在3小时达到最大血浆浓度（Cmax）。第1天首次给药后的青蒿素血浆浓度 - 时间曲线下面积（AUC）和Cmax值比第6天高约6倍。青蒿素血浆浓度的这种下降表明由于明显的自身诱导作用，代谢能力增强。
