Interações de fármacos usados na terapêutica clínica antipsicótica com albumina humana: estudo através de espectrofluorimetria

• Autor(a) principal: Coura, Carla Patricia de Morais e
• Data de Publicação: 2016
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/8604
• topic: Haloperidol; Biperidene; Clonazepam; Spectrometry; Fluorescence; Drugs; interaction; Serum albumin; Haloperidol; Biperideno; Clonazepam; Espectrofluorimetria; Interações de medicamentos; Albumina sérica; Haloperidol; Biperideno; Clonazepam; Espectrofluorimetria; Interações de medicamentos; Albumina sérica; CNPQ::CIENCIAS DA SAUDE

The aim of this study was to make a comparative study of the interactions of drugs haloperidol (HPD), biperiden (BPD) and clonazepam (CNZ) with human and bovine albumin, using the fluorescence suppression technique. This technique uses the natural fluorescence emission of tryptophan present in the amino acid chains of proteins, when excited with light of wavelengths between 290 and 295 nm. The difficulty in predicting the clinical effects of plasma levels of drugs transported by the blood makes the protein binding a parameter of great importance pharmacological and toxicological. The results showed the primary site for HPD and CNZ in albumin may be located in subdomain IB, while the BPD would bind the subdomain IIA. Considering the concentration range for each drug, there are two classes of sites on HSA for HPD and only a class for BPD and CNZ. Among them, only HPD binds forming complex with HSA. In small concentrations, BPD reduces fluorescence of HSA by collisional quenching, but as increased drug concentration also occur static quenching. In the case of CNZ, occurs only collision quenching, for all tested concetrações. For ratio drug/HAS 1/1000, Stern-Volmer constant at 37 ° C for HPD, BPD and CNZ were respectively 2.17 (± 0.05) × 107 M-1 and 2.01 (± 0.03) × 108 M-1, and 2.10 (± 0.04) × 107 M-1. The study of competition for binding sites on HSA by means of titrations of HSA-HPD complex by BPD and CNZ, and the solution HSA content HSA by BPD confirmed that the three drugs do not compete with them for binding sites. However, the interaction of HSA with one (HPD or CNZ) causes conformational changes in the protein structure resulting in increased or decreased accessibility (or internalized) to Trp or binding sites for other drug (BPD or CNZ ).