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Developmental Toxicity Studies with Pregabalin in Rats: Significance of Alterations in Skull Bone Morphology

Pregabalin was administered to pregnant Wistar rats during organogenesis to evaluate potential developmental toxicity. In an embryo‐fetal development study, compared with controls, fetuses from pregabalin‐treated rats exhibited increased incidence of jugal fused to maxilla (pregabalin 1250 and 2500...

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Autores principales: Morse, Dennis C., Henck, Judith W., Bailey, Steven A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585975/
https://www.ncbi.nlm.nih.gov/pubmed/27074409
http://dx.doi.org/10.1002/bdrb.21175
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author Morse, Dennis C.
Henck, Judith W.
Bailey, Steven A.
author_facet Morse, Dennis C.
Henck, Judith W.
Bailey, Steven A.
author_sort Morse, Dennis C.
collection PubMed
description Pregabalin was administered to pregnant Wistar rats during organogenesis to evaluate potential developmental toxicity. In an embryo‐fetal development study, compared with controls, fetuses from pregabalin‐treated rats exhibited increased incidence of jugal fused to maxilla (pregabalin 1250 and 2500 mg/kg) and fusion of the nasal sutures (pregabalin 2500 mg/kg). The alterations in skull development occurred in the presence of maternal toxicity (reduced body weight gain) and developmental toxicity (reduced fetal body weight and increased skeletal variations), and were initially classified as malformations. Subsequent investigative studies in pregnant rats treated with pregabalin during organogenesis confirmed the advanced jugal fused to maxilla, and fusion of the nasal sutures at cesarean section (gestation day/postmating day [PMD] 21) in pregabalin‐treated groups. In a study designed to evaluate progression of skull development, advanced jugal fused to maxilla and fusion of the nasal sutures was observed on PMD 20–25 and PMD 21–23, respectively (birth occurs approximately on PMD 22). On postnatal day (PND) 21, complete jugal fused to maxilla was observed in the majority of control and 2500 mg/kg offspring. No treatment‐related differences in the incidence of skull bone fusions occurred on PND 21, indicating no permanent adverse outcome. Based on the results of the investigative studies, and a review of historical data and scientific literature, the advanced skull bone fusions were reclassified as anatomic variations. Pregabalin was not teratogenic in rats under the conditions of these studies
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spelling pubmed-65859752019-06-27 Developmental Toxicity Studies with Pregabalin in Rats: Significance of Alterations in Skull Bone Morphology Morse, Dennis C. Henck, Judith W. Bailey, Steven A. Birth Defects Res B Dev Reprod Toxicol Original Articles Pregabalin was administered to pregnant Wistar rats during organogenesis to evaluate potential developmental toxicity. In an embryo‐fetal development study, compared with controls, fetuses from pregabalin‐treated rats exhibited increased incidence of jugal fused to maxilla (pregabalin 1250 and 2500 mg/kg) and fusion of the nasal sutures (pregabalin 2500 mg/kg). The alterations in skull development occurred in the presence of maternal toxicity (reduced body weight gain) and developmental toxicity (reduced fetal body weight and increased skeletal variations), and were initially classified as malformations. Subsequent investigative studies in pregnant rats treated with pregabalin during organogenesis confirmed the advanced jugal fused to maxilla, and fusion of the nasal sutures at cesarean section (gestation day/postmating day [PMD] 21) in pregabalin‐treated groups. In a study designed to evaluate progression of skull development, advanced jugal fused to maxilla and fusion of the nasal sutures was observed on PMD 20–25 and PMD 21–23, respectively (birth occurs approximately on PMD 22). On postnatal day (PND) 21, complete jugal fused to maxilla was observed in the majority of control and 2500 mg/kg offspring. No treatment‐related differences in the incidence of skull bone fusions occurred on PND 21, indicating no permanent adverse outcome. Based on the results of the investigative studies, and a review of historical data and scientific literature, the advanced skull bone fusions were reclassified as anatomic variations. Pregabalin was not teratogenic in rats under the conditions of these studies John Wiley and Sons Inc. 2016-04-13 2016-04 /pmc/articles/PMC6585975/ /pubmed/27074409 http://dx.doi.org/10.1002/bdrb.21175 Text en © 2016 The Authors Birth Defects Research Published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Morse, Dennis C.
Henck, Judith W.
Bailey, Steven A.
Developmental Toxicity Studies with Pregabalin in Rats: Significance of Alterations in Skull Bone Morphology
title Developmental Toxicity Studies with Pregabalin in Rats: Significance of Alterations in Skull Bone Morphology
title_full Developmental Toxicity Studies with Pregabalin in Rats: Significance of Alterations in Skull Bone Morphology
title_fullStr Developmental Toxicity Studies with Pregabalin in Rats: Significance of Alterations in Skull Bone Morphology
title_full_unstemmed Developmental Toxicity Studies with Pregabalin in Rats: Significance of Alterations in Skull Bone Morphology
title_short Developmental Toxicity Studies with Pregabalin in Rats: Significance of Alterations in Skull Bone Morphology
title_sort developmental toxicity studies with pregabalin in rats: significance of alterations in skull bone morphology
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585975/
https://www.ncbi.nlm.nih.gov/pubmed/27074409
http://dx.doi.org/10.1002/bdrb.21175
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