title: Effects of the combined artesunate and mefloquine antimalarial drugs on rat embryos.
abstract: Artemisinins combination therapy (ACT) is the first choice therapy for falciparum malaria. Data on the safety of ACTs in pregnancy are limited and controversial and the use is not recommended on the first trimester. To evaluate the effects of isolated and combined artesunate (AS)/mefloquine (MQ) on embryo rats, pregnant rats were treated orally with AS (15 and 40 mg/kg body weight (bwt)/day), MQ (30 and 80 mg/kg bwt/day) and AS/MQ (15/30 and 40/80 mg/kg bwt/day) on days 9-11 post coitum (pc). The dams were euthanized on day 12 pc and gestational and embryos histological parameters were evaluated. Embryolethality and histopathological anomalies were significant when AS was given alone or combined with MQ. Combination of AS and MQ did not enhance their toxicity compared to their separate administrations; on the other side, there was a reduction in the toxic effects of the AS when combined with MQ. Isolated MQ did not induce developmental toxicity.
authors: Department of Pharmacology, Federal University of Paraná, Curitiba, Paraná, Brazil.
authors: A C
authors: AC
authors: Boareto
authors: J C
authors: JC
authors: Müller
authors: E L B
authors: EL
authors: Lourenço
authors: N
authors: N
authors: Lombardi
authors: A C
authors: AC
authors: Lourenço
authors: I
authors: I
authors: Rabitto
authors: R N
authors: RN
authors: de Morais
authors: F S
authors: FS
authors: Rios
authors: P R
authors: PR
authors: Dalsenter
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000633:toxicity*; D037621:Artemisinins / Q000008:administration & dosage / Q000633:toxicity*; D000077332:Artesunate; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D020964:Embryo Loss / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D018811:Maternal Exposure / Q000009:adverse effects*; D015767:Mefloquine / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D015767:Mefloquine
keywords: Artesunate; antimalarial; embryolethality; histopathology; mefloquine