The pharmacokinetics of artemisinin after oral, intramuscular and rectal administration to volunteers.
The pharmacokinetics after oral, intramuscular and rectal administration of artemisinin, a new potent antimalarial drug, to healthy volunteers has been examined. The study was set-up as a four-way cross-over design with a wash-out period of one week between the test days. In ten volunteers artemisinin concentrations in serum were monitored using a reversed phase HPLC assay with UV detection after derivatization. After oral administration, artemisinin was rapidly but incompletely absorbed, the mean absorption time was 0.78 h and the bioavailability relative to the intramuscularly injected suspension in oil 32%. The mean residence time of the latter (10.6 h) was 3 times that of the oral formulation (3.4 h). This seems to enable a twice daily dosage regimen for the intramuscular oil injection, while the oral formulation necessitates a more frequent dosing interval. After intramuscular injection and rectal administration of an aqueous suspension, very low and variable artemisinin concentrations in serum were observed, probably indicating a poor and erratic absorption.
Titulaer
H A
HA
Dept of Pharmaceutics, University of Utrecht, The Netherlands.
Zuidema
J
J
Kager
P A
PA
Wetsteyn
J C
JC
Lugt
C B
CB
Merkus
F W
FW
D000284:Administration, Oral; D000285:Administration, Rectal; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D037621:Artemisinins; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C031327:artemisinin