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Ceska Gynekologie-Czech Gynaecology

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Effect of six antiretroviral drugs (delavirdine, stavudine, lamivudine, nelfinavir, amprenavir and lopinavir/ritonavir in association) on albino pregnant rats (Rattus norvegicus Albinus, Rodentia, Mammalia): biological assay.

Published:1 August 2014 DOI: PMID: 25398151
M U Nakamura, E Araujo Júnior, J M Sim?es, R M Filho Oliveria, L Júnior Kulay

Abstract

Objective: To compare the chronic effects of antiretrovirals (lamivudine, stavudine, delavirdine, nelfinavir, amprenavir and an association of lopinavir/ritonavir) on albino pregnant rats.

Design: Review.

Setting: Department of Obstetrics, Federal University of S?o Paulo (UNIFESP), S?o Paulo, SP, Brazil.

Methods: This was a comparative retrospective study formed by 18 groups of 10 pregnant rats each, which were nearly three months of age and weighed 200 g. All of them were medicated every day using a stomach probe, while the control group was given 1 mL of distilled water. The study groups received lamivudine (at 5, 15 and 45 mg/kg/day); stavudine (at 1, 3 and 9 mg/kg/day); nelfinavir (at 40, 120 and 360 mg/kg/day); amprenavir (at 46, 138 and 414 mg/kg/day); lopinavir/ritonavir (at 12.8/3.2, 38.4/9.6 and 115/28.8 mg/kg/day) and delavirdine (at 20 and 60 mg/kg/day). These represented 1, 3 and 9 times the human therapeutic dose, except for the last drug, for which the 9-times dose was not used. Maternal, litter and placental weights, implantation and reabsorption numbers, major external fetal malformations and fetal and maternal deaths were evaluated. The Kruskal-Wallis test was used to compare quantitative variables and the chi-square test was used to compare qualitative variables.

Results: At all three doses, stavudine increased the maternal weight (p=0.001), while lamivudine at 3- and 9-times doses reduced it (p<0.001). Amprenavir at all of the doses, and lopinavir/ritonavir at 3- and 9-times doses, caused higher rates of maternal death (p<0.001). Regarding the fetuses, none of the antiretroviral drugs studied were harmful with regard to implantation, reabsorption, teratogenity and mortality (p>0.05). Stavudine at all doses reduced the litter weights (p<0.001); however, lamivudine at the usual and 3-times doses, delavirdine at 3-times dose, and amprenavir at 3-times dose increased the litter weight (p<0.001).

Conclusion: In the maternal compartment, we observed lethal toxicity in the pregnant rats that received amprenavir and ritonavir/lopinavir; and maternal weight change with lamivudine and stavudine. In the fetal compartment, adverse effects were observed in relation to litter weight from stavudine, lamivudine, delavirdine and amprenavir.

Substances (6)

Related products
Procduct Name CAS Molecular Formula Supplier Price
Lamivudine 134678-17-4 C8H11N3O3S 762 suppliers $5.00-$2400.00
Stavudine 3056-17-5 C10H12N2O4 525 suppliers $5.00-$1500.00
AMPRENAVIR 161814-49-9 C25H35N3O6S 206 suppliers $28.00-$2691.10
NELFINAVIR 159989-64-7 C32H45N3O4S 108 suppliers Inquiry
DELAVIRDINE 136817-59-9 C22H28N6O3S 101 suppliers $38.00-$5166.00
LOPINAVIR + RITONAVIR (PREMIXED) 1 suppliers Inquiry

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