No 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.

No abstract

The efficacy of artelinic acid and artemisinin, orally administered at 10 and 50 mg kg-1 day-1, was compared in Plasmodium berghei infected mice. Subsequently, the pharmacokinetics of artelinic acid after intravenous, intramuscular, oral and rectal administration of a 20 mg kg-1 aqueous solution to rabbits were studied in a four-way randomized cross-over experiment. After intravenous administration, artelinic acid concentrations in blood plasma were high (C0: 76 +/- 15 mg L-1), and the drug was rapidly eliminated from the central compartment, showing linear elimination kinetics with an elimination half-life of 15 +/- 3 min. A large inter-subject variation appeared in the absorption rate and the extent of absorption (2-92%) over the 120 min interval after intramuscular administration. Also, a large inter-subject variation in individual rectal bioavailability (17-100%) was shown, which was dependent on the site of absorption in the rectum. The estimated oral bioavailability was low (4.6 +/- 1.7%), probably due to a high first-pass effect and possible decomposition in the acidic gastric environment.

Free (0.6 mg), and liposome encapsulated chloroquine (0.6, 3 mg), were injected intraperitoneally, intramuscularly and subcutaneously in mice. Intraperitoneal administration of liposome-encapsulated chloroquine resulted in high and long lasting concentrations of chloroquine in the blood compared with intraperitoneal administration of free chloroquine. After administration of the liposome-encapsulated chloroquine the concentrations in the spleen were also higher, indicating that chloroquine liposomes reached the blood compartment intact after intraperitoneal administration. After intramuscular and subcutaneous administration the chloroquine liposomes acted as a local depot, giving a slower release from the subcutaneous fat layer than from the muscle depot. After the 0.6 mg dose a burst effect was found at about 7 h in most of the animals; this was not found after the 3 mg dose. This finding and the slower release after the 3 mg dose than after the 0.6 mg dose could be explained by the formation of aggregates after the injection.