Localization of artesunate and its derivatives in the pregnant rat and fetus following oral administration and relationship to developmental toxicity.

Background: The antimalarial drug artesunate affects erythroid cells leading to developmental toxicity and adult reticulocytopenia. We report on a kinetic study in rats and the tissue distribution of radioactivity following oral administration of [(3)H]-artesunate to pregnant rats using quantitative whole-body autoradiography (QWBA).

Methods: Rats were dosed orally with chlorproguanil/dapsone/artesunate (including 11.

Developmental toxicity of artesunate in the rat: comparison to other artemisinins, comparison of embryotoxicity and kinetics by oral and intravenous routes, and relationship to maternal reticulocyte count.

Background: The antimalarial, artesunate, is teratogenic and embryolethal in rats, with peak sensitivity on Days 10 and 11 postcoitum (pc).

Methods: We compared the developmental toxicity of structurally related artemisinins, dihdyroartemisinin (DHA), artemether (ARTM), and arteether (ARTE) to that of artesunate after oral administration to rats on Day 10 pc. In separate studies, embryolethality was characterized after single intravenous (IV) administration of artesunate on Day 11 pc, and toxicokinetic parameters following oral and IV administration were compared.