Szczech George M, Wang Laurene H, Walsh John P, Rousseau Franck S
Triangle Pharmaceuticals, Inc, 4611 University Drive, PO Box 50530, Durham, NC 27717, USA.
Reprod Toxicol. 2003 Jan-Feb;17(1):95-108. doi: 10.1016/s0890-6238(02)00098-9.
Reproductive and developmental toxicology studies were conducted with emtricitabine, a nucleoside analog in development for treatment of human immunodeficiency virus (HIV) (Phase III) and hepatitis B (HBV) (Phase III) infections. Oral doses up to 1000 mg/kg/day provided daily area under the curve (AUC(0-->24)) exposure to pregnant animals approximately 60- (mice) to 120-fold (rabbits) higher than that in humans at the recommended dose of 200 mg given once per day. In a mouse fertility study, emtricitabine had no effect on fertility, sperm count, or early embryonic development. There was no increased incidence of malformations in mouse and rabbit embryofetal toxicology studies. The average ratio for concentration of emtricitabine in fetal plasma divided by concentration in maternal plasma was approximately 0.40 in mice and 0.50 in rabbits, a finding that indicates significant exposure of the fetuses to emtricitabine. The development and fertility of F(1) progeny were unaffected by emtricitabine in a mouse pre- and post-natal study. These data demonstrate a favorable pre-clinical reproductive safety profile for emtricitabine.
对恩曲他滨进行了生殖和发育毒理学研究，恩曲他滨是一种正在开发用于治疗人类免疫缺陷病毒（HIV）（III期）和乙型肝炎病毒（HBV）（III期）感染的核苷类似物。口服剂量高达1000mg/kg/天，使怀孕动物的每日曲线下面积（AUC(0→24)）暴露量比人类每天服用一次推荐剂量200mg时高出约60倍（小鼠）至120倍（兔子）。在一项小鼠生育力研究中，恩曲他滨对生育力、精子计数或早期胚胎发育没有影响。在小鼠和兔子的胚胎-胎儿毒理学研究中，畸形发生率没有增加。小鼠胎儿血浆中恩曲他滨浓度与母体血浆中浓度的平均比值约为0.40，兔子约为0.50，这一结果表明胎儿显著暴露于恩曲他滨。在一项小鼠产前和产后研究中，F(1)代后代的发育和生育力不受恩曲他滨影响。这些数据表明恩曲他滨具有良好的临床前生殖安全性。
