Ondansetron and teratogenicity in rats: Evidence for a mechanism mediated via embryonic hERG blockade

被引：11
作者：
Danielsson, B. [1 ]
Webster, William S. [2 ]
Ritchie, Helen E. [3 ]
机构：
[1] Swedish Natl Board Hlth & Welf, Stockholm, Sweden
[2] Univ Sydney, Sydney Med Sch, Discipline Anat & Histol, Sydney, NSW 2006, Australia
[3] Univ Sydney, Sydney Med Sch, Discipline Biomed Sci, Sydney, NSW 2006, Australia
来源：
REPRODUCTIVE TOXICOLOGY | 2018年 / 81卷
关键词：
Ondansetron; Nausea and vomiting in pregnancy; Heart arrhythmia; Birth defects; LONG QT SYNDROME; CARDIOVASCULAR TERATOGENESIS; DEVELOPMENTAL TOXICITY; HEART-RATE; PHARMACOKINETICS; PREGNANCY; DRUG; RISK; DEFECTS; RABBIT;
D O I：
10.1016/j.reprotox.2018.08.018
中图分类号：
Q [生物科学];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
The potent hERG channel blocking drug ondansetron is used off-label for treatment of nausea and vomiting in early pregnancy. Some human epidemiological studies have associated ondansetron with fetal cardiovascular defects and orofacial clefts. This study investigated the effects of ondanestron on embryonic heart rhythm of gestational day (GD) 13 rat embryos in vitro and then integrated the results with published animal teratology, and animal and human pharmacokinetic studies to perform a risk evaluation. Ondansetron caused concentration dependent bradycardia and arrhythmia. Cardiovascular malformations in rats occurred at exposures slightly higher than those in early human pregnancy. Together the results suggest that ondansetron can have teratogenic potential in rats and humans mediated via hERG block and severe heart rhythm disturbances in the embryo. The risk may be increased in human pregnancy if additional risk factors are present such as hypokalemia.
引用
收藏
页码：237 / 245
页数：9
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