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Contribution of the Antiepileptic Drug Administration Regime in the Development and/or Establishment of Pharmacoresistant Epilepsy

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Book cover Pharmacoresistance in Epilepsy

Abstract

Overexpression of membrane transporters is one of the main pharmacokinetic reasons that lead to the lack of response of antiepileptics in drug refractory treatments. The present chapter deals with the difficulty anticonvulsant agents have in reaching the brain receptor sites.

An inducer and substrate of efflux transporter drug, when it is continuously administered so as to maintain constant levels in body fluids could become noneffective throughout time, even it was especially effective for a certain type of epilepsy.

In spite of the fact phenytoin (PHT) is a well-known effective antiepileptic drug with characteristic nonlinear pharmacokinetics; resistance could be developed in epileptic patients during chronic treatments. Some new approaches that challenge conventional assumptions about its peculiar pharmacokinetics were consistent with the mechanism involved in refractory epilepsy.

Salivary drug monitoring was a useful tool for understanding the mechanism of both pharmacokinetics and pharmacoresistance developed by PHT as inducer and substrate of efflux transporters.

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Authors and Affiliations

  1. Pharmaceutical Sciences Department, Universidad de la República, Av. General Flores 2124, Montevideo, 11800, Uruguay

    Pietro Fagiolino, Marta Vázquez, Cecilia Maldonado, Silvana Alvariza & Manuel Ibarra

  2. Medical Research Unit in Neurological Diseases, National Medical Center “Siglo XXI”, IMSS, Hospital of Specialties, Cuauhtemoc No. 330-4, Col. Doctores, Mexico City, Mexico DF, 06720, Mexico

    Sandra Orozco-Suárez Ph.D. & Iris Angélica Feria-Romero Ph.D.

  3. Department of Pharmacobiology, Center for Research and Advanced Studies, Mexico City, Mexico

    Luisa Rocha

Authors
  1. Pietro Fagiolino
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  2. Marta Vázquez
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  3. Sandra Orozco-Suárez Ph.D.
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  4. Cecilia Maldonado
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  5. Silvana Alvariza
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  7. Manuel Ibarra
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  8. Luisa Rocha
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Corresponding author

Correspondence to Pietro Fagiolino .

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Editors and Affiliations

  1. , Pharmacobiology Department, Center for Research and Advanced Studies, Av. Instituto Politécnico Nacional 2508, Mexico City, 07360, Mexico

    Luisa Rocha

  2. , Disciplina de Neurologia Experimental, UNIFESP/EPM, Rua Botucatu 740, São Paulo, 04023-900, Brazil

    Esper A. Cavalheiro

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Fagiolino, P. et al. (2013). Contribution of the Antiepileptic Drug Administration Regime in the Development and/or Establishment of Pharmacoresistant Epilepsy. In: Rocha, L., Cavalheiro, E. (eds) Pharmacoresistance in Epilepsy. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6464-8_11

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