Dien T K, de Vries P J, Khanh N X, Koopmans R, Binh L N, Duc D D, Kager P A, van Boxtel C J
Institute for Clinical Research in Tropical Medicine, Bach Mai Hospital, Hanoi, Vietnam.
Antimicrob Agents Chemother. 1997 May;41(5):1069-72. doi: 10.1128/AAC.41.5.1069.
The influence of food intake on the pharmacokinetics of artemisinin was studied with six healthy Vietnamese male subjects. In a crossover study, artemisinin capsules (500 mg) were administered with and without food after an overnight fast. Plasma samples were obtained up to 24 h after intake of each drug. Measurement of artemisinin concentrations was performed by high-performance liquid chromatography with electrochemical detection. Tolerance was evaluated according to subjective and objective findings, including repeated physical examinations, routine blood investigations, and electrocardiograms. Pharmacokinetics were analyzed with a noncompartmental method and with a one-compartment model. This model had either zero-order or first-order input. No statistically significant differences were found between the results of the two experimental conditions. Specifically, there were no consistent differences in parameters most likely to be affected by food intake, including absorption profile, absorption rate, bioavailability (f) (as reflected in area under the concentration time curve [AUC]), and drug clearance. Some mean +/- standard deviation parameters after food were as follows: maximum concentration of drug in serum (Cmax), 443 +/- 224 microg x liter(-1); time to Cmax, 1.78 +/- 1.2 h; AUC, 2,092 +/- 1,441 ng x ml(-1) x h, apparent clearance/f, 321 +/- 167 liter x h(-1); mean residence time, 4.42 +/- 1.31 h; and time at which half of the terminal value was reached, 0.97 +/- 0.68 h. The total amount of artemisinin excreted in urine was less than 1% of the dose. We conclude that food intake has no major effect on artemisinin pharmacokinetics. In addition, we conclude tentatively that artemisinin is cleared by the liver, that this clearance does not depend on liver blood flow (i.e., that artemisinin is a so-called low-clearance drug), and that absorption of the drug is not affected by food intake.
在6名健康的越南男性受试者身上研究了食物摄入对青蒿素药代动力学的影响。在一项交叉研究中，经过一夜禁食后，分别在有食物和无食物的情况下给予青蒿素胶囊（500毫克）。在摄入每种药物后长达24小时采集血浆样本。采用高效液相色谱电化学检测法测定青蒿素浓度。根据主观和客观检查结果评估耐受性，包括多次体格检查、常规血液检查和心电图检查。采用非房室模型法和一室模型分析法对药代动力学进行分析。该模型具有零级或一级输入。两种实验条件的结果之间未发现统计学上的显著差异。具体而言，在最可能受食物摄入影响的参数方面没有一致的差异，包括吸收曲线、吸收速率、生物利用度（f）（如浓度-时间曲线下面积[AUC]所反映）和药物清除率。进食后一些平均±标准差参数如下：血清中药物的最大浓度（Cmax），443±224微克·升-1；达到Cmax的时间，1.78±1.2小时；AUC，2092±1441纳克·毫升-1·小时，表观清除率/f，321±167升·小时-1；平均驻留时间，4.42±1.31小时；以及达到终末值一半时的时间，0.97±0.68小时。尿中排泄的青蒿素总量不到给药剂量的1%。我们得出结论，食物摄入对青蒿素药代动力学没有重大影响。此外，我们初步得出结论，青蒿素由肝脏清除，这种清除不依赖于肝血流量（即青蒿素是一种所谓的低清除率药物），并且该药物的吸收不受食物摄入的影响。
