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.
Titulaer
H A
HA
Department of Pharmaceutics, Faculty of Pharmacy, University of Utrecht, The Netherlands.
Eling
W M
WM
Zuidema
J
J
D000042:Absorption; D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D037621:Artemisinins; D001682:Biological Availability; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects*; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C062768:artelinic acid; C031327:artemisinin