Effect of food intake on pharmacokinetics of oral artemisinin in healthy Vietnamese subjects.
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.
Dien
T K
TK
Institute for Clinical Research in Tropical Medicine, Bach Mai Hospital, Hanoi, Vietnam.
de Vries
P J
PJ
Khanh
N X
NX
Koopmans
R
R
Binh
L N
LN
Duc
D D
DD
Kager
P A
PA
van Boxtel
C J
CJ
D000284:Administration, Oral; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D037621:Artemisinins; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004435:Eating; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008657:Metabolic Clearance Rate; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014744:Vietnam
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C031327:artemisinin