Developmental toxicity of ibutilide fumarate in rats after oral administration

Teratology
T A Marks, R D Terry

Abstract

In two Segment II Teratology studies, timed-pregnant Crl:CD[BR] (Sprague-Dawley) rats were treated orally (gastric intubation) on days 6-15 of gestation with ibutilide fumarate (ibutilide), a class III antiarrhythmic that has been shown to increase the refractory period and action potential duration of myocardial cells. In the first study, ibutilide does of 20, 40, and 80 mg/kg/ day were tested. Although maternal toxicity was equivocal in the 80 mg/kg/day group, all 23 rats that conceived had entirely resorbed liters when the animals were killed on day 20 of gestation. Similarly, 12 of 24 litters were completely resorbed in the 40 mg/kg/day group, with an 87.7% postimplantational loss. Of the surviving fetuses in this group, 48.6% had at least one malformation. The incidences of malformed pharynx and malformed palate, along with adactyly, were statistically significantly higher in this group than in the control group. In addition, a significant (P < 0.05) increase in total malformations (5.7% of the fetuses), relative to the controls (0.8%), was found for the 20 mg/kg/day group. Since a no observed adverse effect level (NOAEL) was not found, a second teratology study was performed. In this study, the ibutilide doses were 5, 10,...Continue Reading

References

Oct 1, 1992·Regulatory Toxicology and Pharmacology : RTP·D L Black, T A Marks
Mar 15, 1991·Journal of the American College of Cardiology·J P DiMarco
Jun 1, 1974·Teratology·R E Staples, J K Haseman

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Citations

Oct 30, 2015·Expert Review of Cardiovascular Therapy·Jennifer M WrightMichael E Field
Mar 4, 2005·Birth Defects Research. Part A, Clinical and Molecular Teratology·Bengt R DanielssonAnna-Carin Sköld
Jun 23, 2007·Birth Defects Research. Part A, Clinical and Molecular Teratology·Christian DanielssonBengt R Danielsson
Mar 7, 2007·Pacing and Clinical Electrophysiology : PACE·Thomas A BurkartMario D Gonzalez
Feb 12, 2011·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Bruce K BeyerAnthony R Scialli
May 24, 2005·Reproductive Toxicology·Bengt A J KällénBengt R Danielsson
May 29, 2019·Expert Opinion on Pharmacotherapy·Georgios GeorgiopoulosChristodoulos Stefanadis
Nov 7, 2017·Birth Defects Research·Helen E RitchieJaimie W Polson

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