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- Danielsson, Bengt, et al.
(författare)
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Use of ondansetron during pregnancy and congenital malformations in the infant.
- 2014
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 50, s. 134-137
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Tidskriftsartikel (refereegranskat)abstract
- The study investigates teratogenic risks with ondansetron (Zofran(®)). Data from the Swedish Medical Birth Register combined with the Swedish Register of Prescribed Drugs were used to identify 1349 infants born of women who had taken ondansetron in early pregnancy, 1998-2012. Presence of congenital malformations in the offspring was identified with three national health registers. In a Mantel-Haenszel analysis adjustment was made for year of delivery, maternal age, parity, smoking in early pregnancy and pre-pregnancy body mass index. Risks were expressed as odds or risk ratios with 95% confidence intervals. No statistically significantly increased risk for a major malformation was found. The risks for a cardiovascular defect and notably a cardiac septum defect were increased and statistically significant (OR=1.62, 95% CI 1.04-2.14, and RR 2.05, 95% CI 1.19-3.28, respective). The teratogenic risk with ondansetron is low but an increased risk for a cardiac septum defect is likely.
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- Danielsson, Christian, et al.
(författare)
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Exploration of human, rat, and rabbit embryonic cardiomyocytes suggests K-channel block as a common teratogenic mechanism
- 2013
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP): Policy B. - 0008-6363 .- 1755-3245. ; 97:1, s. 23-32
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Tidskriftsartikel (refereegranskat)abstract
- Several drugs blocking the rapidly activating potassium (K-r) channel cause malformations (including cardiac defects) and embryonic death in animal teratology studies. In humans, these drugs have an established risk for acquired long-QT syndrome and arrhythmia. Recently, associations between cardiac defects and spontaneous abortions have been reported for drugs widely used in pregnancy (e.g. antidepressants), with long-QT syndrome risk. To investigate whether a common embryonic adverse-effect mechanism exists in the human, rat, and rabbit embryos, we made a comparative study of embryonic cardiomyocytes from all three species. less thanbrgreater than less thanbrgreater thanPatch-clamp and quantitative-mRNA measurements of K-r and slowly activating K (K-s) channels were performed on human, rat, and rabbit primary cardiomyocytes and cardiac samples from different embryo-foetal stages. The K-r channel was present when the heart started to beat in all species, but was, in contrast to human and rabbit, lost in rats in late organogenesis. The specific K-r-channel blocker E-4031 prolonged the action potential in a species- and development-dependent fashion, consistent with the observed K-r-channel expression pattern and reported sensitive periods of developmental toxicity. E-4031 also increased the QT interval and induced 2:1 atrio-ventricular block in multi-electrode array electrographic recordings of rat embryos. The K-s channel was expressed in human and rat throughout the embryo-foetal period but not in rabbit. less thanbrgreater than less thanbrgreater thanThis first comparison of mRNA expression, potassium currents, and action-potential characteristics, with and without a specific K-r-channel blocker in human, rat, and rabbit embryos provides evidence of K-r-channel inhibition as a common mechanism for embryonic malformations and death.
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- Källén, Bengt, et al.
(författare)
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Fetal safety of erythromycin. An update of Swedish data.
- 2014
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 1432-1041 .- 0031-6970. ; 70:3, s. 355-360
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Tidskriftsartikel (refereegranskat)abstract
- In previous studies from the Swedish Medical Birth Register, a possible association between erythromycin therapy and an increased risk for cardiovascular defects was found. Other studies using different methodology have not verified this observation. The finding resulted in a warning for the use of erythromycin in early pregnancy, followed by a marked decline in such use. The present study was conducted to follow up on the previous observations and to find methodological explanations for the variation in results in these different published studies.
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- Nilsson, Mats F., et al.
(författare)
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Improved methodology for identifying the teratogenic potential in early drug development of hERG channel blocking drugs
- 2010
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Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 29:2, s. 156-163
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Tidskriftsartikel (refereegranskat)abstract
- Drugs blocking the potassium current IKr of the heart (via hERG channel-inhibition) have the potential to cause hypoxia-related teratogenic effects. However, this activity may be missed in conventional teratology studies because repeat dosing may cause resorptions. The aim of the present study was to investigate an alternative protocol to reveal the teratogenic potential of IKr-blocking drugs. The IKr blocker astemizole, given as a single dose (80mg/kg) on gestation day (GD) 13 to pregnant rats caused digital defects. In whole rat embryo culture (2h) on GD 13, astemizole caused a decrease in embryonic heart rate at 20nM, and arrhythmias at 200-400nM. Cetirizine, without IKr-blocking properties, did not affect the rat embryonic heart in vitro. The present study shows that single dose testing on sensitive days of development, together with whole embryo culture, can be a useful methodology to better characterize the teratogenic potential of IKr-blocking drugs.
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