The aim of this study was to evaluate the bioavailability of artesunate (ARTS) and dihydroartemisinin (DHA). When the single-pass isolated perfused rat liver model was used, the hepatic bioavailability of ARTS (39 microM) was 0.20 and the bioavailability of DHA in ARTS and DHA (35 microM) perfusions was 0.12 and 0.11, respectively. Thus, the combined bioavailability of ARTS and DHA in the ARTS perfusions (0.32) was three-fold higher than the bioavailability of DHA. In the human study, eight healthy volunteers were randomized to receive oral ARTS (135 mg; 352 micromol) or oral DHA (120 mg; 422 micromol). The area under the curve (AUC(0-6 hr)) of DHA following ARTS (2.9 micromol x hr/L) was higher than the AUC(0-6 hr) of DHA following DHA administration (1.2 micromol x hr/L; P < 0.005). The dose-corrected relative oral bioavailability of DHA for DHA compared with ARTS was 43%. Thus, the use of conventional oral dosage regimens of ARTS appears preferable to oral administration of DHA.