Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Claritromicina/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores do Citocromo P-450 CYP3A/efeitos adversos , Pirimidinas/metabolismo , Pirimidinas/uso terapêutico , Pirimidinas/farmacocinética , Rabdomiólise/induzido quimicamente , Sulfonamidas/metabolismo , Sulfonamidas/uso terapêutico , Sulfonamidas/farmacocinética , Ácidos Graxos Monoinsaturados/metabolismo , Ácidos Graxos Monoinsaturados/uso terapêutico , Ácidos Graxos Monoinsaturados/farmacocinética , Pravastatina/metabolismo , Pravastatina/uso terapêutico , Pravastatina/farmacocinética , Inibidores de Hidroximetilglutaril-CoA Redutases/metabolismo , Transportadores de Ânions Orgânicos , Transportadores de Ânions Orgânicos Sódio-Independentes/antagonistas & inibidores , Transportador 1 de Ânion Orgânico Específico do Fígado , Interações Medicamentosas , Injúria Renal Aguda/induzido quimicamente , Rosuvastatina Cálcica , Fluorbenzenos/metabolismo , Fluorbenzenos/uso terapêutico , Fluorbenzenos/farmacocinética , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto , Fluvastatina , Hiperpotassemia/induzido quimicamente , Indóis/metabolismo , Indóis/uso terapêutico , Indóis/farmacocinéticaRESUMO
The purpose of this study is to determine the population pharmacokinetics of 3 statins after oral dosing. This was achieved by simultaneous data fitting of 101 different individuals from three studies: 25 subjects for pravastatin, 40 subjects for simvastatin and 36 subjects for atorvastatin. Each study was fitted separately. Plasma profiles were best characterized by 1 -compartment model for pravastatin, 2-compartment model for simvastatin, and 3 -compartment model for atorvastatin. The criteria used for model building involved the examination of the fitted cuves, the improvement in objective function and statistical tests: Akaike test, Schwarz test and log likelihood test; and examining the improvement in residual plots. The elimination rate constant and clearance values for pravastatin is higher than simvastatin and higher than atorvastatin which is in agreement with models used. The variability, as indicated by population coefficient of variation, is generally higher than 30% rendering them highly variable drugs