The pharmacokinetics of artemisinin after oral, intramuscular and rectal administration to volunteers

Abstract

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.

The pharmacokinetics of artemisinin after administration of two different suppositories to healthy Vietnamese subjects.

“…Contrary to a previous study in which preliminary data on rectal dosage are discussed, 4 we found that therapeutic concentrations were reached. This is in agreement with the effectiveness of rectally administered artemisinin in malaria as reported in several studies.…”

“…In the treatment of severe and complicated malaria, parenteral administration of drugs is usually necessary, and rectal administration could be a feasible alternative, especially in remote areas. Although in one preliminary pharmacokinetic study very low, and probably subtherapeutic plasma concentrations were reported after rectal dosage 4 , clinical trials with artemisinin or artesunate suppositories in severe malaria have shown good results. [5][6][7][8] We therefore determined the pharmacokinetics of artemisinin suppositories that are presently available in Vietnam; these suppositories have been used in recent therapeutic trials.…”

Artemisinin for treatment of uncomplicated falciparum malaria: is there a place for monotherapy?

“…Artemisinin is rapidly but incompletely absorbed, and its plasma elimination halflife is short (2.6 hr). 1,2 This rapid elimination is probably one of the reasons why monotherapy is associated with high recrudescence rates.…”

Artemisia scoparia – A new source of artemisinin

“…Artemisinin is the new and promising drug which is also active against resistant plasmodium malaria ( McIntosh and Olliaro, 2004). Extensive work on the production of artemisinin from plant of A. annua has been done (Actona and Klayman, 1985;El-Sohly, 1990;Jha et al, 1988;Janick, 1996a, 1996b;Ferreira et al, 1994;Simon, 1995a, 1995b;Theoharides et al, 1988;Titulaer et al, 1990). Artemisinin has also been reported from tissue culture of this plant (Jha et al, 1988;Fulzele et al, 1991;Jaziri, 1995;Martinez and Staba, 1992;Nair et al, 1986;Van Nieuwerburgh et al, 2006) and biochemical as well as molecular approaches for enhanced production of artemisinin from A. annua has also been tried (Abdin et al, 2003;Van Nieuwerburgh et al, 2006 …”