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Ondansetron and teratogenicity in rats: Evidence for a mechanism mediated via embryonic hERG blockade.
Reprod Toxicol. 2018 10; 81:237-245.RT

Abstract

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.

Authors+Show Affiliations

Swedish National Board of Health and Welfare, Stockholm, Sweden. Electronic address: Bengt.Danielsson@socialstyrelsen.se.Discipline of Anatomy and Histology, Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: bill.webster@sydney.edu.au.Discipline of Biomedical Sciences, Sydney Medical School, The Unvieristy of Sydney, Sydney, NSW 2006, Australia. Electronic address: helen.ritchie@sydney.edu.au.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30149139

Citation

Danielsson, B, et al. "Ondansetron and Teratogenicity in Rats: Evidence for a Mechanism Mediated Via Embryonic hERG Blockade." Reproductive Toxicology (Elmsford, N.Y.), vol. 81, 2018, pp. 237-245.
Danielsson B, Webster WS, Ritchie HE. Ondansetron and teratogenicity in rats: Evidence for a mechanism mediated via embryonic hERG blockade. Reprod Toxicol. 2018;81:237-245.
Danielsson, B., Webster, W. S., & Ritchie, H. E. (2018). Ondansetron and teratogenicity in rats: Evidence for a mechanism mediated via embryonic hERG blockade. Reproductive Toxicology (Elmsford, N.Y.), 81, 237-245. https://doi.org/10.1016/j.reprotox.2018.08.018
Danielsson B, Webster WS, Ritchie HE. Ondansetron and Teratogenicity in Rats: Evidence for a Mechanism Mediated Via Embryonic hERG Blockade. Reprod Toxicol. 2018;81:237-245. PubMed PMID: 30149139.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ondansetron and teratogenicity in rats: Evidence for a mechanism mediated via embryonic hERG blockade. AU - Danielsson,B, AU - Webster,William S, AU - Ritchie,Helen E, Y1 - 2018/08/24/ PY - 2018/03/17/received PY - 2018/08/23/revised PY - 2018/08/23/accepted PY - 2018/8/28/pubmed PY - 2018/12/12/medline PY - 2018/8/28/entrez KW - Birth defects KW - Heart arrhythmia KW - Nausea and vomiting in pregnancy KW - Ondansetron SP - 237 EP - 245 JF - Reproductive toxicology (Elmsford, N.Y.) JO - Reprod. Toxicol. VL - 81 N2 - 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. SN - 1873-1708 UR - https://www.unboundmedicine.com/medline/citation/30149139/Ondansetron_and_teratogenicity_in_rats:_Evidence_for_a_mechanism_mediated_via_embryonic_hERG_blockade_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0890-6238(18)30097-2 DB - PRIME DP - Unbound Medicine ER -