Variable patterns in anticonvulsant drug-induced malformations in mice: comparisons of phenytoin and phenobarbital.
Anticonvulsant drugs are known to induce a varied pattern of malformation in both humans and in experimental rodent models. Often the clinical overlap between the pattern of defects induced by different anticonvulsant drugs is so striking that many clinicians question the role these compounds play relative to the existing maternal seizure disorder in the etiology of the observed malformations. In three inbred mouse strains exposed to phenytoin or phenobarbital in utero, the pattern of malformation differed markedly. From the types of anomalies observed, it is apparent that phenobarbital induced more malformations, while phenytoin produced a higher frequency of anomalies related to incomplete development. Thus, while there exists a certain degree of similarity between some of the minor features characteristic of each drug-induced syndrome, there are distinct differences in pregnancy outcome in experimental animals exposed to these drugs. Given the fact that phenobarbital induces more malformations that can be traced to exposure during early organogenesis, it may be wise to consider a therapeutic strategy in which phenytoin is utilized only during organogenesis, and is then replaced with phenobarbital for the remainder of the pregnancy.
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced; D051379:Mice; D008815:Mice, Inbred Strains; D010634:Phenobarbital / Q000097:blood / Q000633:toxicity*; D010672:Phenytoin / Q000097:blood / Q000633:toxicity*; D011247:Pregnancy; D013045:Species Specificity
D010672:Phenytoin; D010634:Phenobarbital