PMID- 30149139
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20181211
IS  - 1873-1708 (Electronic)
IS  - 0890-6238 (Linking)
VI  - 81
DP  - 2018 Oct
TI  - Ondansetron and teratogenicity in rats: Evidence for a mechanism mediated via 
      embryonic hERG blockade.
PG  - 237-245
LID - S0890-6238(18)30097-2 [pii]
LID - 10.1016/j.reprotox.2018.08.018 [doi]
AB  - 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.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Danielsson, B
AU  - Danielsson B
AD  - Swedish National Board of Health and Welfare, Stockholm, Sweden. Electronic 
      address: Bengt.Danielsson@socialstyrelsen.se.
FAU - Webster, William S
AU  - Webster WS
AD  - Discipline of Anatomy and Histology, Sydney Medical School, The University of 
      Sydney, Sydney, NSW 2006, Australia. Electronic address: 
      bill.webster@sydney.edu.au.
FAU - Ritchie, Helen E
AU  - Ritchie HE
AD  - Discipline of Biomedical Sciences, Sydney Medical School, The Unvieristy of 
      Sydney, Sydney, NSW 2006, Australia. Electronic address: 
      helen.ritchie@sydney.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180824
PL  - United States
TA  - Reprod Toxicol
JT  - Reproductive toxicology (Elmsford, N.Y.)
JID - 8803591
RN  - 0 (Antiemetics)
RN  - 0 (Ether-A-Go-Go Potassium Channels)
RN  - 0 (Teratogens)
RN  - 4AF302ESOS (Ondansetron)
SB  - IM
MH  - Abnormalities, Drug-Induced/etiology
MH  - Animals
MH  - Antiemetics/pharmacokinetics/*toxicity
MH  - Cardiovascular Abnormalities/chemically induced
MH  - Embryo, Mammalian/abnormalities/drug effects
MH  - Ether-A-Go-Go Potassium Channels/*antagonists & inhibitors
MH  - Female
MH  - Heart/drug effects
MH  - Humans
MH  - Ondansetron/pharmacokinetics/*toxicity
MH  - Pregnancy
MH  - Rats, Sprague-Dawley
MH  - Teratogens/pharmacokinetics/*toxicity
OTO - NOTNLM
OT  - Birth defects
OT  - Heart arrhythmia
OT  - Nausea and vomiting in pregnancy
OT  - Ondansetron
EDAT- 2018/08/28 06:00
MHDA- 2018/12/12 06:00
CRDT- 2018/08/28 06:00
PHST- 2018/03/17 00:00 [received]
PHST- 2018/08/23 00:00 [revised]
PHST- 2018/08/23 00:00 [accepted]
PHST- 2018/08/28 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2018/08/28 06:00 [entrez]
AID - S0890-6238(18)30097-2 [pii]
AID - 10.1016/j.reprotox.2018.08.018 [doi]
PST - ppublish
SO  - Reprod Toxicol. 2018 Oct;81:237-245. doi: 10.1016/j.reprotox.2018.08.018. Epub 
      2018 Aug 24.