Pharmacokinetics of artemisinin and artesunate after oral administration in healthy volunteers.
This study was designed to determine the pharmacokinetic parameters of a new pharmaceutical form of artemisinin (a natural substance extracted from the Artemisia annua L. plant) and of one of its derivatives, artesunate, a semisuccinate of 12-hydroxy-artemisinin. These two compounds are widely used in the treatment of malaria. The new oral forms of these two compounds, in 250-mg tablets, were used in two parallel pharmacokinetic studies. For artemisinin, the mean pharmacokinetic parameters were maximum drug concentration (Cmax) = 0.36 microgram/ml; peak time (tmax) = 100 min; appearance half-life (t1/2 max) = 0.62 hr; distribution half-life (t1/2 alpha) = 2.61 hr; decline half-life (t1/2 beta) = 4.34 hr; and total area under the concentration-time curve (AUC) = 1.19 micrograms.hr/ml. For artesunate, its main metabolite, dihydroartemisinin, was measurable in the plasma. The mean pharmacokinetic parameters for dihydroartemisinin were appearance rate constant (Ka) = 2.11 hr-1; elimination rate constant (Ke) = 1.18 hr-1; biotransformation half-life = 0.33 hr; elimination half-life = 0.65 hr; and AUC = 0.74 microgram.hr/ml. Both pharmaceutical forms were well-tolerated and no undesirable side effects were observed in any of the subjects.
Benakis
A
A
Department of Pharmacology, University Medical Centre, Geneva, Switzerland.
Paris
M
M
Loutan
L
L
Plessas
C T
CT
Plessas
S T
ST
D000284:Administration, Oral; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D037621:Artemisinins; D000077332:Artesunate; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D013607:Tablets; D000077332:Artesunate; C039060:artenimol; C031327:artemisinin