Pharmacokinetic and pharmacodynamic aspects of artelinic acid in rodents.

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.