RESUMO
Abrocitinib is approved to treat moderate-to-severe atopic dermatitis and eliminated mainly through cytochrome P450 (CYP450) enzyme. Two commonly used antidepressants, amitriptyline and fluoxetine, could inhibit the activities of CYP2C19 and CYP3A4. In this study, we developed a new and quick ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for quantitatively analyzing the plasma concentration of abrocitinib, and further investigated the effects of amitriptyline or fluoxetine on the pharmacokinetics of abrocitinib in rats. The selectivity, linearity, recovery, accuracy, precision, matrix effect and stability of UPLC-MS/MS assay were satisfied according to the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. Our result showed that when co-administered with amitriptyline and fluoxetine, the CLz/F of abrocitinib was reduced by 44.4 % and 33.3 %, respectively, while the AUC(0-t) of abrocitinib was increased by 77.7 % and 49.4 %, respectively. It indicated that amitriptyline and fluoxetine could significantly increase the plasma concentration of abrocitinib in rats. Thus, dose adjustment of abrocitinib may be required when it is combined with amitriptyline or fluoxetine in ongoing clinical practice.
Assuntos
Amitriptilina , Fluoxetina , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Animais , Fluoxetina/farmacocinética , Fluoxetina/farmacologia , Ratos , Masculino , Amitriptilina/farmacocinética , Antidepressivos/farmacocinética , Antidepressivos/farmacologia , Cromatografia Líquida de Alta Pressão , Interações Medicamentosas , Pirimidinas/farmacocinética , Pirimidinas/farmacologia , Pirimidinas/sangueRESUMO
ABSTRACT Interactions between herbs and drugs may increase or decrease the pharmacological or toxicological effects of either component. Experimental data on the pharmacokinetic interactions between herbal products and drugs are limited. This study attempted to investigate the effect of Bacopa monnieri Linn. (Brahmi) formulation on the pharmacokinetics of amitriptyline in rats. In this study, rats were randomly divided into two groups (n = 6 each) which were served as a control (amitriptyline alone) and treatment group (amitriptyline with B. monnieri), respectively. Rats in the treatment group received B. monnieri (31 mg/kg/day) whereas the control group received normal saline by oral gavage for seven days before a single intragastric administration of 25 mg/kg amitriptyline. Plasma concentrations of amitriptyline were measured up to 24 h after its administration by a developed and validated high-performance liquid chromatography method. Pretreatment with B. monnieri produced a significant increase in the maximum plasma concentration (Cmax), area under the curve (AUC0-t) and elimination half-life (t1/2) of amitriptyline by 16.8%, 26.5%, and 15.5%, respectively, compared to amitriptyline alone. Moreover, oral clearance and volume of distribution (Vss) were decreased by 26.2% and 15.5% respectively. This study concluded that B.monnieri significantly enhanced the oral bioavailability of amitriptyline in rats.
Assuntos
Animais , Masculino , Ratos , Bacopa/efeitos adversos , Interações Medicamentosas , Amitriptilina/farmacocinética , Plantas Medicinais/classificação , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Neste artigo é exposto sucintamente aspectos do metabolismo dos antidepressivos tricíclicos (desmetilaçao e hipdroxilaçao) que devem ser levados em conta na interpretaçao das dosagens plasmáticas e efeitos clínicos destes medicamentos
Assuntos
Humanos , Masculino , Feminino , Amitriptilina/farmacocinética , Antidepressivos Tricíclicos/farmacologia , Antidepressivos Tricíclicos/metabolismo , Clomipramina/farmacocinética , Desipramina/farmacocinética , Doxepina/farmacocinética , Imipramina/farmacocinética , Maprotilina/farmacocinética , Mianserina/farmacocinética , Nortriptilina/farmacocinética , Protriptilina/farmacocinética , Viloxazina/farmacocinéticaRESUMO
Discute aspectos relevantes à compreensão dos mecanismos por meio dos quais os anticonvulsivantes de segunda geração podem atuar no controle da dor de origem neurópatica.(AU)