Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

BACKGROUND: Artesunate is a commonly used antimalarial drug derived from artemisinin. It is rapidly converted to dihydroartemisinin. Little is known on this conversion in the GI tract and blood, and how this influences absorption. In order to study the absorption phase of the kinetics of artesunate following oral administration in rats, samples were collected at baseline, and then 0.5, 2, 5, 10, 15, 30, 45, 60 and 120 minutes after a single dose of 150 mg. RESULTS: Peak concentration of parent artesunate and dihydroartemisinin was achieved within 5 and 37.5 +/- 8.7 min, respectively of start of administration through gavage. The half lives of absorption were 2.73 +/- 0.85 and 12.49 +/- 2.49 min, respectively. CONCLUSIONS: These times were considerably shorter for artesunate than those found in studies which start sampling later. The profiles of parent compound and metabolite result from a complex equation dictated by the pH-dependent rates of hydroxylation of artesunate to dihydroartemisinin, the different rates at which either compounds are absorbed, and the catalytic hydroxylation by esterases. The rate of chemical oxidation of artesunate is pH dependent; this explains its rapid conversion to dihydroartemisinin in the stomach, as compared to its greater stability in other compartments at higher pH and in plasma. We propose that variable proportions of absorption take place in the stomach, and conclude that parent artesunate reaches an early peak within minutes of dosing, and that the early dihydroartemisinin levels result primarily from the absorption of the metabolite as such.

Original publication

DOI

10.1186/1471-2210-1-12

Type

Journal

BMC Pharmacology

Publication Date

01/2001

Volume

1

Addresses

UNPD/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), CDS, World Health Organization, 20, avenue AppiaCH-1211 Geneva 27, Switzerland. olliarop@who.int

Keywords

Animals, Rats, Rats, Sprague-Dawley, Sesquiterpenes, Artemisinins, Antimalarials, Administration, Oral, Intestinal Absorption, Half-Life, Male