Influence of mefloquine administration during early pregnancy on rat embryonic development

Mefloquine (MQ) is a potent effective antimalarial drug against multiple drug-resistant Plasmodium falciparum. It has been proved that MQ can be given safely during the second and third trimesters. However, there is very limited information on the drug safety during the first trimester. The aim of the present work was to investigate the embryotoxicity and teratogenicity of MQ during critical periods of early development. Wistar rats were orally administered with a single dose of MQ (45 mg/kg bwt or 187 mg/kg bwt) on the 1st, 6th or 13th days of pregnancy. Cyclophosphamide (CPA) was chosen as a positive control. On the 21st day of gestation, standard parameters of reproductive performance and fetal examination were estimated. Malondialdehyde (MDA) level, glutathione reductase activity and glutathione (GSH) content were evaluated in placenta and liver homogenates of mothers and fetuses. The results indicated that MQ did not adversely affect the number of implantation, resorption, litter size and fetal body weight and length. Only groups treated with MQ on the 1st day of gestation exhibited significant decrease in fetal body weight. Examination of fetuses for external, visceral and skeletal changes showed minimal variations involving extension of lateral brain ventricles and renal pelvis and signs of delayed ossification. These variations were accompanied with significant elevation of MDA level and reduction of GSH content of fetal liver. Prenatal exposure to MQ at early pregnancy did not cause any embryolethal or teratogenic effect. It could slightly exacerbate minor variations.