Effect of food intake on pharmacokinetics of oral artemisinin in healthy Vietnamese subjects

Abstract

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.

Artemisinins as potential anticancer agents: uptake detection in erythrocytes using Fourier transform infrared spectroscopy and cytotoxicity against bladder cancer cells

“…First, as the concentrations of the artemisinin derivatives present are far smaller and much harder to identify within a mixture, a range of different concentrations more closely approximating to clinically achievable plasma values than used here should be applied to cells to assess the concentration limits for detection. Among the highest human plasma concentrations reported in the literature is 443 ng/mL20 compared with the 1 mg/mL applied to the washed erythrocytes in vitro here. Second, a range of cell lines could be used to demonstrate differences in uptake and detection.…”

Simulated digestion of dried leaves of Artemisia annua consumed as a treatment (pACT) for malaria

“…Although a pharmacokinetic study by Dien et al (1997) showed that food intake did not affect AN absorption after oral consumption of pure AN, assessment of the impact of food is critical to understanding how dried leaves are digested. To determine the effect of food, common dietary components such as sugar (sucrose), four oils, and three cereal meals were included in digestion tests.…”

Development of a Specific Monoclonal Antibody for the Quantification of Artemisinin in Artemisia annua and Rat Serum

“…29 In all these studies, the half-life of artemisinin is short (~30 min in rats, ~2 h in humans), 31, 32 which might be due to rapid metabolism and elimination by the liver and to a lesser extent by other organs such as lungs and kidneys. 36 In human, artemisinin is metabolized in the liver by cytochrome P450s including CYP2B6 and CYP3A4, 37 yielding a number of metabolites that are excreted in urine, 38 while urinary excretion of unchanged artemisinin is negligible 31 . The low C max may also partially be due to irreversible decomposition by erythrocytic heme, 39 and binding to serum albumin 40 .…”