Ujházy E, Onderová E, Horáková M, Bencová E, Durisová M, Nosál R, Balonová T, Zeljenková D
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Czechoslovakia.
Pharmacol Toxicol. 1989 Mar;64(3):286-90. doi: 10.1111/j.1600-0773.1989.tb00648.x.
Teratological studies of the hypolipidaemic drugs etofylline clofibrate (VULM) and fenofibrate were carried out in mice. Pregnant mice were given etofylline clofibrate and fenofibrate in doses 11.7, 117.1, and 585.5 mg/kg orally from day 7 to 16 of gestation. Terminal maternal body weight was significantly decreased after all doses of etofylline clofibrate in a non-dose-related fashion compared to the control group. The foetuses were examined on day 19 of gestation. They were weighed and inspected for external, skeletal and visceral abnormalities. The low and middle doses of etofylline clofibrate and fenofibrate had no adverse effects on embryofoetal development. The highest etofylline clofibrate dose induced a significant decrease of foetal weight at term, likewise postimplantation loss was significantly increased after the highest dose of fenofibrate. The incidence of external, skeletal and visceral anomalies was not dose-dependent. In this study no teratogenic effects were detected, yet with the highest etofylline clofibrate and fenofibrate doses some foetotoxic effects were observed.
对降血脂药物益多酯(VULM)和非诺贝特进行了小鼠致畸学研究。从妊娠第7天至第16天,给怀孕小鼠口服剂量为11.7、117.1和585.5mg/kg的益多酯和非诺贝特。与对照组相比,所有剂量的益多酯给药后,孕鼠终末体重均以非剂量相关方式显著降低。在妊娠第19天对胎儿进行检查。对其称重并检查外部、骨骼和内脏异常情况。低剂量和中剂量的益多酯和非诺贝特对胚胎-胎儿发育无不良影响。益多酯的最高剂量导致足月时胎儿体重显著降低,同样,非诺贝特的最高剂量给药后着床后丢失率也显著增加。外部、骨骼和内脏异常的发生率与剂量无关。在本研究中未检测到致畸作用,但在益多酯和非诺贝特最高剂量时观察到了一些胚胎毒性作用。