Extended administration of the association of zidovudine plus ritonavir during rat pregnancy: maternal and fetal effects.
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.
Pereira Fontes
T M
TM
Federal University of São Paulo School of Medicine (UNIFESP-EPM), São Paulo, Brazil.
Santos Simões
R
R
Martins Oliveira
F H
FH
de Jesus Simões
M s
Ms
Oliveira-Filho
R M
RM
Nakamura
M U
MU
Kulay
L
L
D000818:Animals; D019380:Anti-HIV Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005317:Fetal Growth Retardation / Q000139:chemically induced; D005327:Fetal Resorption / Q000139:chemically induced; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D019438:Ritonavir / Q000633:toxicity*; D015430:Weight Gain / Q000187:drug effects*; D015215:Zidovudine / Q000633:toxicity*
D019380:Anti-HIV Agents; D015215:Zidovudine; D019438:Ritonavir