RESUMO
Absorption rate analysis (ARA) was introduced in 2011 as a no-cost investigative tool for elucidating the details of drug absorption recorded in individual plasma time-concentration profiles. The method continues to be refined since its introduction, so that a new article offering more advanced applications of the method is appropriate. The stomach has been observed to exert considerable influence on the drug absorption process beyond the usual issues of drug solubility and stability in the gastric environment. This article is intended to demonstrate how readers can use ARA to reveal common factors affecting drug absorption. A newly introduced technique is to make observations concerning individual subjects, then assemble those individual observations to reveal factors not observable on an individual basis. This technique considerably increases the utility of ARA for revealing potential barriers to drug absorption.
Assuntos
Absorção Gástrica/fisiologia , Mucosa Gástrica/metabolismo , Preparações Farmacêuticas/sangue , Ensaios Clínicos Fase I como Assunto , Relação Dose-Resposta a Droga , Estabilidade de Medicamentos , Duodeno/metabolismo , Esvaziamento Gástrico/fisiologia , Humanos , Absorção Intestinal/fisiologia , Complexo Mioelétrico Migratório/fisiologia , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/química , Solubilidade , Estômago/efeitos dos fármacos , Comprimidos com Revestimento EntéricoAssuntos
Anticolesterolemiantes/farmacocinética , Medicamentos Genéricos/farmacocinética , Ezetimiba/farmacocinética , Adulto , Anticolesterolemiantes/administração & dosagem , Área Sob a Curva , Estudos Cross-Over , Composição de Medicamentos , Medicamentos Genéricos/administração & dosagem , Ezetimiba/administração & dosagem , Voluntários Saudáveis , Humanos , Masculino , Equivalência Terapêutica , Adulto JovemRESUMO
Since the 1980s, a considerable body of research has been dedicated to the development of in silico models for the prediction of human pharmacokinetic data based on absorption in a series of discreet intestinal compartments. While some of these models have been successfully used to predict future pharmacokinetic results or to explain previous results, evidence for compartmental absorption in individual pharmacokinetic data has not been published. This article presents in vivo evidence for compartmental drug absorption along with an empirical method for determining gastrointestinal (GI) tract location during absorption, using individual time-absorption rate profiles. Comparisons are shown between the absorption rate profiles and corresponding gamma scintigraphy images, to demonstrate the reliability of the GI position assignments and a hypothesis is proposed to explain the appearance of peaks and troughs in absorption rate profiles. Absorption rate analysis is shown to be a reliable and low cost tool for interpretation of unexpected pharmacokinetic data. Pharmaceutical scientists should find it useful for understanding the in vivo performance of drug products and it is hoped this will result in fewer delays and lower costs during drug development programs.
