Efectos de los inductores antiepilépticos en la neuropsicofarmacología: una cuestión ignorada. Parte II: cuestiones farmacológicas y comprensión adicional

León, José de

doi:10.1016/j.rpsm.2014.10.005

Cited by 27 publications

(3 citation statements)

References 147 publications

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“…Furthermore, after both single-and multiple-dose administration, simulations did not show a relevant change in drug CL, even when autoinduction mechanisms were integrated in the model. Although some of the literature highlights that phenytoin induces its own metabolism using CYP2C9 and CYP2C19 after multiple-dose administrations [34], the clinical effect of phenytoin autoinduction has been debatable [73,74]. Our PBPK model supports the latter, with accurate simulation of both single-and multiple-dose studies using the model without autoinduction.…”

Section: Discussionmentioning

confidence: 55%

Comprehensive Physiologically Based Pharmacokinetic Model to Assess Drug–Drug Interactions of Phenytoin

Rodriguez-Vera,

Yin,

Almoslem

et al. 2023

Pharmaceutics

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Regulatory agencies worldwide expect that clinical pharmacokinetic drug–drug interactions (DDIs) between an investigational new drug and other drugs should be conducted during drug development as part of an adequate assessment of the drug’s safety and efficacy. However, it is neither time nor cost efficient to test all possible DDI scenarios clinically. Phenytoin is classified by the Food and Drug Administration as a strong clinical index inducer of CYP3A4, and a moderate sensitive substrate of CYP2C9. A physiologically based pharmacokinetic (PBPK) platform model was developed using GastroPlus® to assess DDIs with phenytoin acting as the victim (CYP2C9, CYP2C19) or perpetrator (CYP3A4). Pharmacokinetic data were obtained from 15 different studies in healthy subjects. The PBPK model of phenytoin explains the contribution of CYP2C9 and CYP2C19 to the formation of 5-(4′-hydroxyphenyl)-5-phenylhydantoin. Furthermore, it accurately recapitulated phenytoin exposure after single and multiple intravenous and oral doses/formulations ranging from 248 to 900 mg, the dose-dependent nonlinearity and the magnitude of the effect of food on phenytoin pharmacokinetics. Once developed and verified, the model was used to characterize and predict phenytoin DDIs with fluconazole, omeprazole and itraconazole, i.e., simulated/observed DDI AUC ratio ranging from 0.89 to 1.25. This study supports the utility of the PBPK approach in informing drug development.

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Section: Discussionmentioning

confidence: 55%

Comprehensive Physiologically Based Pharmacokinetic Model to Assess Drug–Drug Interactions of Phenytoin

Rodriguez-Vera,

Yin,

Almoslem

et al. 2023

Pharmaceutics

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“…Uma reação adversa identificada no estudo foi a diminuição da eficácia, envolvendo principalmente os benzodiazepínicos, que poderia ser explicada pela indução do citocromo P450, especificamente, as famílias CYP3A e CYP2C, enzimas responsáveis pelo aumento do metabolismo e que podem ser responsáveis pela auto indução, diminuindo o efeito do próprio fármaco e induzindo o metabolismo de outros fármacos administrados concomitantemente (17). (18).…”

Section: Resultsunclassified

Cuidados Farmacêuticos a Pacientes Pediátricos Com a Síndrome Congênita Do Zika Vírus

Rocha

Júnior

Medeiros

et al. 2021

Infarma

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A Síndrome Congênita do Zika Vírus é uma importante enfermidade que emergiu no Brasil no ano de 2015 e não existe cura para esta síndrome. O tratamento medicamentoso visa melhorar a qualidade de vida dos portadores desta doença; entretanto, a terapia medicamentosa com o uso de múltiplos fármacos pode acarretar efeitos adversos e interações medicamentosas. O objetivo do trabalho foi realizar o cuidado farmacêutico com os pacientes pediátricos portadores da Síndrome Congênita do Zika Vírus. Trata-se de um garanestudo longitudinal realizado na Clínica de Fisioterapia da Universidade Estadual da Paraíba e no Centro Especializado em Reabilitação, ambos localizados na cidade de Campina Grande, PB, durante 8 meses. Foram 5 atendimentos por pacientes pediátricos, um a cada mês, utilizando a metodologia Phamacoterapy WorKup e a base de dados Micromedex®. No total, foram avaliados 23 pacientes, 29 prescrições e 71 medicamentos pertencentes a 9 classes farmacológicas. Os anticonvulsivantes foram os mais prescritos. Quanto à comorbidade existente, 8 pacientes apresentaram duas ou mais doenças etiologicamente relacionadas. Houve 35 (49,2%) interações medicamento-medicamento, destas, 8 (22,9%) com efeito grave, 23 (65,7%) moderado, 4 (11,4%) menor e nenhuma contraindicada, além de 32 interações medicamentoalimento e 43 medicamento-laboratório. Os problemas relacionados aos medicamentos identificados foram 42; a ineficácia [23 (55%)] sendo o mais frequente. Portanto, é fundamental o acompanhamento farmacoterapêutico aos pacientes pediátricos portadores da Síndrome Congênita do Zika Vírus para avaliar o uso racional destes medicamentos, no qual o Cuidado Farmacêutico pode fazer a diferença na utilização segura e adequada dos fármacos.

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“…The metabolism of drugs is mainly determined by the effect of the enzymes of the group of CYP. [3][4][5][6] Epilepsy is one of the most prevalent neurological disorders worldwide, affecting approximately 70 million people in the world and at least 5 million of them are in Latin America. The general prevalence of epilepsy in Colombia is 11.3 per 1,000.…”

Section: Introductionmentioning

confidence: 99%

Stevens-Johnson syndrome: relation with phenytoin and carbamazepine associated with HLA and CYP polymorphism in Colombia

Parga-Lozano¹,

Santodomingo²

2021

PPIJ

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The genetic polymorphisms of the Human Leukocyte Antigens (HLA) and Cytochromes P450 (CYP) CYP2C19 and CYP2C9 have been proposed as key elements for susceptibility to antiepileptic drugs such as Phenytoin (PHT) and Carbamazepine (CBZ). These hepatic isoenzymes and HLA´s exhibit genetic polymorphism with interindividual variability in catalytic activity. Stevens-Johnson Syndrome (SJS) is one of the idiosyncratic adverse effects related to PHT and CBZ. The aim of this work is to relate the polymorphisms of the HLA and CYP alleles with the Stevens-Johnson syndrome caused by phenytoin and carbamazepine in the Amerindian population of Colombia.Methodology: A systematic search was carried out in Clinical Key, Pro Quest and PubMed, the results were tabulated and organized according to their expression to be analyzed by means of the MEGA7 software, using Allele Frequencies to know the allelic frequency of HLA in the Colombian Amerindian population.

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Efectos de los inductores antiepilépticos en la neuropsicofarmacología: una cuestión ignorada. Parte II: cuestiones farmacológicas y comprensión adicional

Cited by 27 publications

References 147 publications

Comprehensive Physiologically Based Pharmacokinetic Model to Assess Drug–Drug Interactions of Phenytoin

Comprehensive Physiologically Based Pharmacokinetic Model to Assess Drug–Drug Interactions of Phenytoin

Cuidados Farmacêuticos a Pacientes Pediátricos Com a Síndrome Congênita Do Zika Vírus

Stevens-Johnson syndrome: relation with phenytoin and carbamazepine associated with HLA and CYP polymorphism in Colombia

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