Transdermal artelinic acid: an effective treatment for Plasmodium berghei-infected mice.
Artelinic acid, a derivative of the naturally occurring antimalarial artemisinin, has been incorporated into a gel suitable for transdermal administration. The formulation was tested for efficacy in Plasmodium berghei-infected mice for both curative and prophylactic properties by application to their partially denuded backs, beginning on days 3 and 0, respectively, after injection of parasitized erythrocytes. In the curative experiments, rapid elimination of the parasitemia and 60-day survival of five of five mice was achieved by dermal application of gel containing 0.9 mg of artelinic acid that was administered twice a day, beginning on day 3 after infection, for three days (total dosage of 270 mg/kg). In the prophylactic trials, the establishment of parasitemia was prevented and 60-day survival was achieved in five of five mice at a dose of 0.9 mg of artelinic acid administered twice a day, beginning on the day of inoculation, for two days (total dosage of 180 mg/kg). The transdermal medium, with or without drug, caused no topical or systemic toxicity.
Klayman
D L
DL
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC.
Ager
A L
AL
Fleckenstein
L
L
Lin
A J
AJ
D000279:Administration, Cutaneous; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D037621:Artemisinins; D005782:Gels; D008288:Malaria / Q000188:drug therapy* / Q000517:prevention & control; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects*; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000627:therapeutic use*
D000962:Antimalarials; D037621:Artemisinins; D005782:Gels; D012717:Sesquiterpenes; C062768:artelinic acid