NDLI: 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.

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Sensitive periods for developmental toxicity of orally administered artesunate in the rat.

Embryotoxicity of artesunate in animal species related to drug tissue distribution and toxicokinetic profiles.

Artesunate: developmental toxicity and toxicokinetics in monkeys.

State of the art in developmental toxicity screening methods and a way forward: a meeting report addressing embryonic stem cells, whole embryo culture, and zebrafish.

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.

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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.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Clark, Robert L. Lerman, Steven A. Cox, Estella M. Gristwood, William E. White, Tacey E. K.
Description	Country affiliation: United States Author Affiliation: Clark RL ( GlaxoSmithKline, King of Prussia, Pennsylvania 19406-0939, USA.)
Abstract	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. Lastly, to determine whether maternal hematologic effects occurred at doses that affect embryonic erythroblasts, artesunate was orally administered on Day 11 pc at a dose that caused 100% embryolethality. RESULTS: All artemisinins caused the same pattern of embryolethality and fetal cardiovascular and skeletal abnormalities as previously shown for artesunate. In the IV study, marked postimplantation loss occurred at 1.5 and 3 mg/kg artesunate, but not at 0.75 mg/kg. Among the toxicokinetic parameters evaluated, only the DHA AUC(0-t) was similar at embryolethal oral and IV doses of artesunate. An embryolethal dose of artesunate caused a 15% decrease in maternal reticulocyte counts and no other hematologic effects. CONCLUSIONS: Several structurally related artemisinins cause similar developmental toxicity, suggesting an artemisinin class effect. Equally embryotoxic oral and IV treatments of one artemisinin compound (artesunate) produced similar systemic exposure to the artesunate metabolite, DHA, suggesting that DHA may be the proximate developmental toxicant. Embryolethal doses of artesunate only caused minor changes in maternal reticulocyte counts indicating that adult hematology parameters are not as sensitive as embryonic erythroblasts.
File Format	HTM / HTML
ISSN	15429733
Issue Number	4
Volume Number	83
e-ISSN	15429741
Journal	Birth Defects Research Part B: Developmental and Reproductive Toxicology
Language	English
Publisher	Wiley
Publisher Date	2008-08-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Teratology Discipline Toxicology Artemisinins Pharmacokinetics Toxicity Embryo, Mammalian Drug Effects Prenatal Exposure Delayed Effects Blood Reticulocytes Administration, Oral Animals Administration & Dosage Cesarean Section Drug Administration Routes Embryo Loss Chemically Induced Female Fetus Injections, Intravenous Pregnancy Rats Reticulocyte Count Cytology Comparative Study Journal Article
Content Type	Text
Resource Type	Article
Subject	Developmental Biology Health, Toxicology and Mutagenesis Toxicology Embryology

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