Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Anatomy, Birjand University of Medical Sciences, Birjand, Iran ; Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2013 Oct;16(10):1065-70.
OBJECTIVE(S): Anti-epileptic drugs (AEDs) have the potential to affect fetal development throughout pregnancy. Considering the broad therapeutic indications of pregabalin (PGB), its potential teratogenic effects and the levels of homocysteine have been studied.
Timed-pregnant mice received one of three doses of PGB (20, 40 or 80 mg/kg/day) or the vehicle control during organogenesis, intraperitoneally. The litters were stained and examined for malformations. Total homocysteine (tHcy) was measured in serum from the pregnant mice on GD18.
The rate of fetus malformations increased significantly in all treated groups as compared to the control group. The abnormalities included limb, vertebral column and craniofacial abnormalities. The most common abnormality was limb deformity. The percentage of fetal resorption significantly increased at higher doses. There was no significant difference in tHcy concentrations between the treated and control groups.
Pregabalin may have potential teratogenic effects even in lower doses, however with less intensity than other AEDs. Therefore, it is suggested that great caution should be taken when prescribing it in pregnancy and further investigation for possible mechaninsms.
抗癫痫药物(AEDs)在整个怀孕期间都有可能影响胎儿发育。鉴于普瑞巴林(PGB)的广泛治疗适应症,已经研究了其潜在的致畸作用和同型半胱氨酸水平。
在器官发生期间,经时间妊娠的小鼠通过腹膜内给予三种剂量的 PGB(20、40 或 80mg/kg/天)或载体对照。对幼仔进行染色并检查畸形。在 GD18 时测量来自怀孕小鼠的血清总同型半胱氨酸(tHcy)。
与对照组相比,所有治疗组的胎儿畸形发生率均显着增加。异常包括肢体、脊柱和颅面异常。最常见的异常是肢体畸形。较高剂量的胎儿吸收率显着增加。治疗组和对照组之间的 tHcy 浓度没有显着差异。
普瑞巴林即使在较低剂量下也可能具有潜在的致畸作用,但强度低于其他 AEDs。因此,建议在怀孕期间谨慎使用,并进一步研究可能的机制。