RESUMO
An amperometric drug metabolism biosensor consisting of cytochrome P450-3A4 (CYP3A4) encapsulated in a didodecyldimethylammonium bromide (DDAB) vesicular system on a Pt disk electrode was developed for the determination of indinavir, a protease inhibitor antiretroviral drug. Cyclic, square wave and pulse voltammetric responses of the bioelectrode showed quasi-reversible electrochemistry of the Fe(3+)/Fe(2+) redox species of the heme thiolate CYP3A4 enzyme under aerobic and anaerobic conditions. The biosensor exhibited excellent response to indinavir with a detection limit and response time of 6.158 x 10(-2)mgL(-1), and 40s, respectively. The detection limit is well below the plasma concentration of indinavir (8h after intake) which range from 0.13 to 8.6mgL(-1).
Assuntos
Técnicas Biossensoriais/métodos , Inibidores da Protease de HIV/metabolismo , Inibidores da Protease de HIV/uso terapêutico , Indinavir/metabolismo , Indinavir/uso terapêutico , Aerobiose , Anaerobiose , Técnicas Biossensoriais/instrumentação , Ensaios Clínicos Fase I como Assunto , Citocromo P-450 CYP3A/química , Eletricidade , Eletroquímica , Eletrodos , Enzimas Imobilizadas , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/química , Indinavir/química , Estrutura Molecular , Oxirredução , Platina/química , Compostos de Amônio Quaternário/química , Prata/química , Compostos de Prata/química , Água/químicaAssuntos
Acetilcolina/fisiologia , Piscadela/fisiologia , Córtex Cerebral/fisiologia , Condicionamento Clássico/fisiologia , Neurônios/fisiologia , Estimulação Acústica , Potenciais de Ação/efeitos dos fármacos , Animais , Atropina/farmacologia , Piscadela/efeitos dos fármacos , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Antagonistas Muscarínicos/farmacologia , Neurônios/efeitos dos fármacos , RatosRESUMO
This study concerns the pharmacokinetic behaviour and cardiovascular effects of rapid infusions of hypoxoside (CAS 83643-94-1) and rooperol (CAS 83644-00-2) in anaesthetised Chacma baboons. Institutional approval was obtained and animal care conformed to international guidelines. Hypoxoside (500 mg) and rooperol (240 mg) dissolved in isotonic saline were infused during 15 min. Concentration-time data from high performance liquid chromatography of arterial blood samples were subjected to non-linear curve-fitting to obtain two-compartment mammillary pharmacokinetic models. Mean values were: [Table: see text] Hypoxoside was eliminated without significant metabolite formation and it revealed no cardiovascular effects. Rooperol was metabolized rapidly with formation of nine metabolites of which the major three were the diglucuronide, disulphate and mixed glucuronide sulphate. Rooperol caused moderate, transient increased cardiac output, stroke volume and vascular pressures without increased heart rate or filling pressures, suggestive of increased myocardial contractility probably allied to its catechol structure.
