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Teratogenicity of antiepileptic drugs: role of pharmacogenomics

Raman Sankar1, Jason T Lerner

  • 1David Geffen School of Medicine at UCLA, Mattel Children's Hospital at UCLA, Los Angeles, California 90095-1752, USA.

International Review of Neurobiology
|October 22, 2008
PubMed

Insights

Individualizing antiepileptic drug teratogenic risk requires understanding drug chemistry and host genetics. Research into toxin-scavenging systems and DNA microchip technology can help predict and reduce risks during pregnancy.

Area of Science:

  • Pharmacology
  • Genetics
  • Toxicology

Background:

  • Teratogenic potential of antiepileptic drugs (AEDs) is influenced by drug molecule chemistry and host genetic factors.
  • Hepatic mixed function oxidase systems are implicated in AED teratogenicity.
  • Toxin-scavenging systems like epoxide hydrolase and glutathione reductase may mitigate teratogenic risk.

Purpose of the Study:

  • To explore the interplay of chemical and genetic factors in AED-induced teratogenicity.
  • To highlight the role of genetic variability in detoxification pathways on teratogenic outcomes.
  • To advocate for personalized risk assessment for AEDs in pregnant patients.

Main Methods:

  • Review of existing literature on AED teratogenicity.
  • Analysis of the role of specific enzyme systems (e.g., MFO, epoxide hydrolase) in drug metabolism and detoxification.
  • Discussion of emerging technologies like DNA microchip technology for genetic profiling.

Main Results:

  • Host genetic variability significantly influences the type and severity of teratogenic outcomes.
  • Enzyme systems involved in toxin scavenging play a crucial role in modifying teratogenic risk.
  • Current knowledge is incomplete, necessitating further research.

Conclusions:

  • Personalized risk assessment for AEDs during pregnancy is crucial.
  • Integrating genetic information with drug properties can improve patient safety.
  • Future research and technologies like DNA microchips hold promise for novel interventions to reduce teratogenic potential.

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