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Headache ; 52(5): 765-72, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22435741

RESUMO

OBJECTIVES/BACKGROUND: (1) To investigate whether a parsimonious model for sumatriptan pharmacokinetics can apply to oral administration; (2) for a successful model, whether a monoamine oxidase A inhibitor (MAOI-A) perturbs it; and (3) whether such a model is generalizable to oral almotriptan. These goals respond to statements in US product labeling. METHODS: Extension of a previous model for subcutaneous sumatriptan. Numerical solutions to 3 concurrent differential equations were found, with prospective criteria for model acceptance based upon comparison with clinically observed data. RESULTS: The model was successfully extended by inserting a time factor into the absorption phase. This extension was robust: it imitated clinical data for 3 oral sumatriptan dose sizes (both without and with a concomitant MAOI-A) and also for oral almotriptan. CONCLUSION: A model for oral sumatriptan pharmacokinetics can be found using the differential calculus, and it is generalizable to oral almotriptan. The model suggests that an MAOI-A probably has greater effect on elimination kinetics than first-pass metabolism, and that this interaction appears to be overstated in product labeling.


Assuntos
Transtornos de Enxaqueca/tratamento farmacológico , Monoaminoxidase/metabolismo , Agonistas do Receptor 5-HT1 de Serotonina/administração & dosagem , Sumatriptana/administração & dosagem , Triptaminas/administração & dosagem , Administração Oral , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Masculino , Transtornos de Enxaqueca/enzimologia , Modelos Biológicos , Fatores de Tempo
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