Nakamura M U, Araujo Júnior E, Simões J M, Oliveria R M Filho, Kulay L Júnior
Ceska Gynekol. 2014 Aug;79(4):295-304.
To compare the chronic effects of antiretrovirals (lamivudine, stavudine, delavirdine, nelfinavir, amprenavir and an association of lopinavir/ritonavir) on albino pregnant rats.
Review.
Department of Obstetrics, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
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.
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).
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.
比较抗逆转录病毒药物（拉米夫定、司他夫定、地拉韦啶、奈非那韦、安普那韦以及洛匹那韦/利托那韦合剂）对白化病妊娠大鼠的慢性影响。
综述。
巴西圣保罗圣保罗联邦大学（UNIFESP）妇产科。
这是一项比较性回顾性研究，由18组组成，每组10只妊娠大鼠，年龄近三个月，体重200克。所有大鼠每天使用胃管给药，而对照组给予1毫升蒸馏水。研究组接受拉米夫定（剂量分别为5、15和45毫克/千克/天）；司他夫定（剂量分别为1、3和9毫克/千克/天）；奈非那韦（剂量分别为40、120和360毫克/千克/天）；安普那韦（剂量分别为46、138和414毫克/千克/天）；洛匹那韦/利托那韦（剂量分别为12.8/3.2、38.4/9.6和115/28.8毫克/千克/天）以及地拉韦啶（剂量分别为20和60毫克/千克/天）。这些剂量分别相当于人类治疗剂量的1倍、3倍和9倍，但最后一种药物未使用9倍剂量。评估母鼠、胎仔和胎盘重量、着床和吸收数量、主要外部胎儿畸形以及胎儿和母鼠死亡情况。采用Kruskal-Wallis检验比较定量变量，采用卡方检验比较定性变量。
在所有三个剂量水平下，司他夫定都增加了母鼠体重（p = 0.001），而3倍和9倍剂量的拉米夫定降低了母鼠体重（p < 0.001）。所有剂量的安普那韦以及3倍和9倍剂量的洛匹那韦/利托那韦导致母鼠死亡率更高（p < 0.001）。关于胎儿，所研究的抗逆转录病毒药物在着床、吸收、致畸性和死亡率方面均无有害影响（p > 0.05）。所有剂量的司他夫定都降低了胎仔体重（p < 0.001）；然而，常规剂量和3倍剂量的拉米夫定、3倍剂量的地拉韦啶以及3倍剂量的安普那韦增加了胎仔体重（p < 0.001）。
在母鼠方面，我们观察到接受安普那韦以及利托那韦/洛匹那韦的妊娠大鼠存在致命毒性；拉米夫定和司他夫定导致母鼠体重变化。在胎儿方面，观察到司他夫定、拉米夫定、地拉韦啶和安普那韦对胎仔体重有不良影响。
