ritonavir and Fetal-Resorption

The purpose of the study was to evaluate at term, the effects of the association of zidovudine/ritonavir administered during the entire period of rat pregnancy. Forty pregnant EPM-1 Wistar rats were divided randomly into four groups: one control (drug vehicle control, n=10) and three experimental treated with an oral solution of zidovudine/ritonavir (Exp 1 = 10/20 mg/kg bw, n = 10; Exp 2 = 30/60 mg/kg bw, n=10; Exp 3 = 90/180 mg/kg bw, n=10) from day 0 up to day 20 of pregnancy. Maternal body weights were recorded at the start of the experiment and at the 7th, 14th and the 20th day thereafter. At term (20th day) the rats were anesthetized and, upon laparotomy and hysterotomy, the number of implantations, resorptions, living fetuses, placentae and intrauterine deaths were recorded. The collected fetuses and placentae were weighed, and the concepts were examined under a stereoscopic microscope for external malformations. The maternal body gain and the mean fetal weight at term were both significantly lower (p < 0.01 and p < 0.0001, respectively) in the experimental groups compared to the control. The recorded resorptions were higher in Exp 2 and Exp 3 groups than in the control group. The other parameters were not affected. The exposure of pregnant rats at term to a 1:2 association of zidovudine plus ritonavir resulted in a significant reduction in maternal body weight gain and increased rate of fetal resorption.

Topics: Animals; Anti-HIV Agents; Body Weight; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fetal Development; Fetal Growth Retardation; Fetal Resorption; Pregnancy; Random Allocation; Rats; Rats, Wistar; Ritonavir; Weight Gain; Zidovudine

In view of the very important role played by ritonavir in the prevention of maternal-fetal HIV-vertical transmission, the aim of this experimental study was to evaluate its possible effects on several important obstetric parameters. Ritonavir was administered daily to three groups of pregnant rats (E1 = 20 mg/kg; E2 = 60 mg/kg; E3 = 180 mg/kg; n = 10 in every group) from 'zero' up to the 20th day of pregnancy. Controls (n = 10) were injected with the drug vehicle (propyleneglycol) in the same schedule. We evaluated the effects on fetal and maternal weight gain, placental weight, number of implantations and resorptions, malformations, fertility rate, and maternal and fetal death rates. Body weight gain of the E3 group was significantly lower than that of the other groups, most likely due to a toxic effect of the highest dose of ritonavir. Ritonavir did not affect the number of implantations. Group E3 had five resorptions and some reduction in fertility. The mortality rate was significantly affected by ritonavir (2/10 maternal deaths in E2 and 4/10 in E3). On the other hand, no alterations were observed in the fetuses, a finding which could be due at least in part to the protective action of placental P-glycoprotein.

Topics: Animals; Female; Fetal Resorption; HIV Protease Inhibitors; Infertility, Female; Pregnancy; Random Allocation; Rats; Rats, Wistar; Ritonavir; Weight Gain