title: The evaluation of radiolabeled artesunate on tissue distribution in rats and protein binding in humans.
abstract: The present study reports the tissue distribution, pharmacokinetics, mass balance, and elimination of [(14)C] artesunate (AS) following single intravenous administration in rats. Protein binding was performed with rat and human plasma. Radioactivity and drug levels in blood, plasma, tissues, urine, and feces up to 192 hours were collected and measured. The mean terminal half-life of plasma (76 h) and blood (105 h) radioactivity was prolonged compared with that of unchanged AS (0.43 h) and dihydroartemisinin (0.75 h), an active metabolite of AS. Drug was widely distributed after 1 hour in select tissues. After 24 hours, the radioactivity rapidly declined in all tissues except spleen until 96 hours. Only 1% of total radioactivity was detected in brain tissue. AS revealed a higher binding capacity with human and rat plasma proteins (73-81%). The radioactivity in whole blood was higher (two to fourfold) than that in plasma throughout the period of the treatment, suggesting that AS binding to RBCs may relate to its powerful antimalarial activity.
authors.affiliation: Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland 20307, USA. qigui.li@na.amedd.army.mil
authors.forename: Qigui
authors.initials: Q
authors.lastname: Li
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Xie
authors.forename: Adam
authors.initials: A
authors.lastname: Haeberle
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Peter
authors.initials: P
authors.lastname: Weina
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D000077332:Artesunate; D001345:Autoradiography; D001773:Blood Cells / Q000378:metabolism; D004347:Drug Interactions / Q000528:radiation effects*; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D037621:Artemisinins; D012717:Sesquiterpenes; D000077332:Artesunate