Developmental toxicity studies of lumefantrine and artemether in rats and rabbits
| Autor: | Robert L, Clark, Maureen, Youreneff, Anthony M, DeLise |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
Fluorenes Lumefantrine Dose-Response Relationship Drug Embryonic Development Artemisinins Rats Toxicokinetics Fetal Development Rats Sprague-Dawley Antimalarials Disease Models Animal Ethanolamines Maternal Exposure Pregnancy Toxicity Tests Animals Drug Therapy Combination Female Artemether Rabbits Malaria Falciparum |
| Zdroj: | Birth defects research. Part B, Developmental and reproductive toxicology. 107(6) |
| ISSN: | 1542-9741 |
| Popis: | The combination of artemether plus lumefantrine is a type of artemisinin-based combination therapy (ACT) recommended by the World Health Organization for uncomplicated falciparum malaria except in the first trimester of pregnancy. The first trimester restriction was based on the marked embryotoxicity in animals (including embryo death and cardiac and skeletal malformations) of artemisinins such as artesunate, dihydroartemisinin, and artemether. Before recommending ACTs for use in the first trimester, the World Health Organization has requested that all information relevant to the assessment of risk of ACTs to the embryo be made available to the public. This report describes the results of embryo-fetal development studies of artemether alone, lumefantrine alone, and the combination in rats and rabbits as well as toxicokinetic studies of lumefantrine in pregnant rabbits. The developmental no-effect levels for lumefantrine were 300 mg/kg/day in rats (based on a 25% decrease in litter size at 1000 mg/kg/day) and 1000 mg/kg/day in rabbits. The calculated safety margins based on human equivalent dose and plasma C |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text