Effects of chronic amprenavir treatment on rat pregnancy - Revista Brasileira de Ginecologia e Obstetrícia

OBJECTIVE: to evaluate the chronic effects of amprenavir on implantations, reabsorptions, fetuses, placentae, and maternal and fetal mortality in the albino rat. METHODS: five groups of EPM-1 Wistar pregnant rats were used: two controls: Contr1 (control of stress) and Contr2 (drug vehicle control), and 3 experimental groups that were treated once a day throughout gestation with 46mg/kg (Exper1), 138mg/kg (Exper2) and 414mg/kg (Exper3) of oral solution of amprenavir. The drug and the vehicle (propyleneglycol) were administered by gavage. The evaluations included maternal body weight gain, number of implantations, reabsorptions, fetuses, placentae and of intrauterine deaths as well as fetal and placental mean weight and major malformations. Fragments of lungs, kidneys, liver and intestines were collected and prepared for histopathological evaluation. RESULTS: Exper3 group tended to show lesser maternal body weight gain during gestation (P = 0.07), but amprenavir did not affect the intrauterine contents. The cytotoxic effect of the drug was observed with regard to the histopathological analyses of pregnant rat viscerae and to the maternal mortality rate: 50% in Exper1 and Exper2 groups, and 70% in Exper3 group. CONCLUSION: amprenavir exerted adverse side effects on maternal lung, gut, kidney and liver, and significantly increased maternal mortality rates in all administered doses and especially at 414 mg/kg.