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Administration of lopinavir/ritonavir association during rat pregnancy: maternal and fetal effects
L. Kulay Jr.1,*, C.C. Hagemann1, M.U. Nakamura1, R.S. Simões Simões2, A. Moreira de Carvalho3, R.M. Oliveira-Filho4, S. Espiridião5
1 Department of Obstetrics and Gynecology, Sao Paulo Federal University, School of Medicine (UNIFESP-EPM), São Paulo (SP)
2 Sao Paulo University, Faculty of Medicine (FMUSP), São Paulo (SP)
3 Department of Internal Medicine, School of Medicine, Jose do Rosario Vellano University, Alfenas (MG)l
4 Department of Pharmacology, Institute of Biomedical Sciences, São Paulo University (USP), São Paulo (SP)
5 Department of Obstetrics and Pediatrics, ABC Medical Foundation (FUABC), São Paulo (SP) (Brazil)
Clin. Exp. Obstet. Gynecol. 2013, 40(1), 151–154;
Published: 10 March 2013
Purpose: To evaluate the effects of the association of lopinavir and ritonavir administered during the whole period of rat pregnancy. Methods: 62 Wistar rats of the EPM-1 variant weighing about 200 g were randomly divided into five groups: two controls (Ctr1 = stress control, n = 10; and Ctr2 = drug vehicle control, n = 10) and three experimental ones which were treated with an oral solution of lopinavir/ritonavir (Exp1 = 12.8/3.2 mg/kg b.w., n = 14; Exp2 = 38.4/9.6 mg/kg b.w., n = 14; Exp3 = 115.2/28.8 mg/kg b.w., n = 14) from ‘day 0’ up to the 20th day of pregnancy. Maternal body weight was recorded at the start of the experiment and on the 7th, 14th and 20th day thereafter. At term (20th day), upon laparotomy and hysterotomy, the rats were anesthetized and the amount of implantations, reabsorptions, living fetuses, placentae and intrauterine deaths were recorded. The collected fetuses and placentae were weighed and the concepts were examined under a stereoscope microscope for external malformations. Results: An apparent dose-unrelated lethal effect of the antiviral association on the pregnant rats was observed; notwithstanding, the body weight gain of the surviving rats had no changes, independent of the considered group. It was noted that the quantitative and qualitative intrauterine content of living term rats was indistinguishable from that of the controls. Conclusion: There was some degree of deleterious effects of the administration of the lopinavir/ritonavir association on pregnant rats; such effects eventually led to maternal death. However, neither the surviving rats showed toxicity nor did their concepts present any detectable change which could be related to the drug association.