Effects of the association zidovudine plus ritonavir on the liver and kidneys of pregnant rats. Morphological and biochemical aspects.

PURPOSE: To evaluate biochemical and morphological effects on rats submitted to three different doses of the association zidovudine and ritonavir administered throughout pregnancy. METHODS: Forty pregnant EPM-1 Wistar rats weighing about 200 g were randomly divided into the control group (Ctr = drug vehicle control, n = 10) and three experimental ones which were treated with an oral solution of zidovudine/ritonavir (Exp1 = 10/20 mg/kg bw, n = 10; Exp2 = 30/60 mg/kg bw, n = 10; Exp3 = 90/180 mg/kg bw, n = 10) from 'day 0' up to the 20th day of pregnancy. At term (20th day) the rats were anesthetized. Blood and fetal and maternal organ samples (livers and kidneys) were taken for morphological and biochemical analyses. RESULTS: Upon histological examinations fetal livers and kidneys appeared normal. In contrast the maternal samples revealed structural alterations. Maternal kidneys of the three experimental groups exhibited progressive and dose-dependent histological alterations; liver alterations were detected only in Exp3. Blood levels of AST and ALT were not significantly different from the control group but urea and creatinine levels were lower in groups Exp3 and Exp1. CONCLUSIONS: The administration of zidovudine plus ritonavir throughout rat pregnancy can cause morphological as well as functional changes in maternal kidneys.

Chronic action of association of zidovudine, lamivudine and ritonavir on pregnant rats. A biologic assay.

PURPOSE: To evaluate at term the effects of a highly active antiretroviral (HAAR) drug association administered during the entire period of rat pregnancy. METHODS: Three groups (n = 10 each) of adult pregnant rats were treated with an oral solution of HAAR (Exp 1 = 10/5/20 mg/kg b.w.; Exp 2 = 30/15/60 mg/kg b.w.; Exp 3 = 90/45/180 mg/kg b.w.) from day "0" up to the 20th day of pregnancy. A fourth group served as a control. At term (20th day) the rats were killed under deep anesthesia and the number of implantations, resorptions, living fetuses, placentae and intrauterine deaths were recorded. RESULTS: The highest HAAR doses caused lower maternal weight gain, lower litter weights, and lower placental weights compared to the control group. CONCLUSIONS: HAAR during the entire period of rat pregnancy can reduce maternal body weight gain and lower term placental weight.