The pharmacokinetics of artemisinin after administration of two different suppositories to healthy Vietnamese subjects

被引:19
作者
Koopmans, R
Ha, LD
Duc, D
Dien, TK
Kager, PA
Khanh, NX
Van Boxtel, CJ
De Vries, PJ
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Clin Pharmacol, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Dept Pharmacotherapy, NL-1105 AZ Amsterdam, Netherlands
[3] Univ Amsterdam, Acad Med Ctr, Div Infect Dis Trop Med & AIDS, NL-1105 AZ Amsterdam, Netherlands
[4] Bach Mai Hosp, Inst Clin Res Trop Med, Hanoi, Vietnam
[5] Inst Malariol Parasitol & Entomol, Hanoi, Vietnam
关键词
D O I
10.4269/ajtmh.1999.60.244
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
, Eight healthy Vietnamese male subjects received 400 mg artemisinin formulated into fatty suppositories (FS), and six different subjects received 500 mg of artemisinin formulated in polyethylene glycol suppositories (PEGS). Plasma concentrations were measured by high-performance liquid chromatography with electrochemical detection; concentration versus time curves were analyzed with nonparametric methods. No statistically significant differences were found between the two formulations. The maximum concentration (Cmax) was 100 +/- 102 mu g/L (mean +/- SD, range = 24-330) mu g/L (FS), the pharmacokinetic lag time (Tlag) was 1.3 +/- 1.0 hr (range = 0-3) (FS), and the time of the maximum concentration (Tmax) was 7.1 +/- 2.1 hr (range 3-10) hr (FS). Because artemisinin is nor available for intravenous dosage, absolute bioavailability cannot be assessed. However, compared with a pre vious study on oral artemisinin in healthy Vietnamese subjects, bioavailability relative to oral administration was estimated to be approximately 30%. We conclude that therapeutic blood concentrations of artemisinin can be reached after rectal dosage. The dose after rectal administration should probably be higher than after oral administration; doubling or tripling the oral dose might be necessary, which would imply a rectal dose of at least 20 mg/kg of body weight given twice a day,
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页码:244 / 247
页数:4
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