Plasmodium berghei: the antimalarial action of artemisinin and sodium artelinate in vivo and in vitro, studied by flow cytometry.
Sodium artelinate, a new water-soluble and relatively stable derivative of artemisinin, and its parent compound were tested for their antimalarial action. Experiments were done in vitro with synchronous cultures of Plasmodium berghei. The inhibition of growth by different concentrations of sodium artelinate and artemisinin was determined using flow cytometry. In vivo testing was done by subcutaneous injection of each drug in mice infected with P. berghei. Sodium artelinate, being stable in aqueous solution, was also administered orally to infected mice by its addition to their drinking water. Comparison of the parent compound and the derivative showed that sodium artelinate was slightly less active than artemisinin both in culture and in vivo. However, after oral administration of sodium artelinate, parasites were cleared from the blood with one-half to one-tenth of the dose used in the experiments with subcutaneous injection. The number of mice which were cured by oral administration of sodium artelinate was greater than after subcutaneous injection, even with a total oral dose lower than the injected dose.
Laboratory of Parasitology, Medical Faculty, University of Leiden, The Netherlands.
P H
PH
van Vianen
D L
DL
Klayman
A J
AJ
Lin
C B
CB
Lugt
A L
AL
van Engen
H J
HJ
van der Kaay
B
B
Mons
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D037621:Artemisinins; D004247:DNA / Q000096:biosynthesis; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005434:Flow Cytometry; D007279:Injections, Subcutaneous; D008288:Malaria / Q000097:blood / Q000188:drug therapy*; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000962:Antimalarials; D037621:Artemisinins; D004365:Drugs, Chinese Herbal; D012717:Sesquiterpenes; C062768:artelinic acid; D004247:DNA; C031327:artemisinin