EFFECT OF FOOD-INTAKE ON PHARMACOKINETICS OF ORAL ARTEMISININ IN HEALTHY VIETNAMESE SUBJECTS

The influence of food intake on the pharmacokinetics of artemisinin wa s studied with six healthy Vietnamese male subjects. In a crossover st udy, 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 w as performed by high-performance liquid chromatography with electroche mical detection, Tolerance was evaluated according to subjective and o bjective findings, including repeated physical examinations, routine b lood investigations, and electrocardiograms. Pharmacokinetics,were ana lyzed with a noncompartmental method and with a one-compartment model, This model had either zero-order or first-order input. No statistical ly significant differences were found between the results of the two e xperimental conditions. Specifically, there were no consistent differe nces in parameters most likely to be affected by food intake, includin g absorption profile, absorption rate, bioavailability (f) (as reflect ed in area under the concentration time curve [AUG]), and drug clearan ce, Some mean +/- standard deviation parameters after food were as fol lows: maximum concentration of drug in serum (C-max), 443 +/- 224 mu g .liter(-1); time to C-max, 1.78 +/- 1.2 h; AUG, 2,092 +/- 1,441 ng.ml( -1).h, apparent clearance/f, 321 +/- 167 liter.h(-1); mean residence t ime, 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 concl ude tentatively that artemisinin is cleared by the liver, that this cl earance 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 n ot affected by food intake.