Effects of protein-calorie malnutrition on drug metabolism in vitro by high performance liquid chromatography

Abstract

Protein-calorie malnutrition can be developed from inadequate food intake as well as a consequence of a disease, such as cancer, AIDS, gastrointestinal diseases or tuberculosis. Several studies have demonstrated that malnutrition alters drugs metabolism and availability. These alterations result in changes of drug absorption, protein binding, hepatic metabolism and renal clearance. However, up to now, scarce or even no information exists to specifically address the malnutrition impact on drugs metabolism, which are administrated to treat important diseases in developing countries, such as neurocysticercosis, malaria, tuberculosis and Chaga’s disease. Furthermore, before any biotransformation study it is necessary the development of analytical methods in order to quantify the target drugs in biological fluids. Thus, it is of ultimate interest the development of analytical methods to evaluate the effects of protein-calorie malnutrition on the chiral/achiral drugs metabolism so that development of new compounds, or even adequation of the clinical administration of drugs, can be assisted. High Performance Liquid Chromatography (HPLC) is an analytical technique widely used to analyze drugs in biological fluids, and thus it will be explored in this work. Therefore, the main goal of the proposed work is to conduct in vitro studies in order to evaluate the protein-calorie malnutrition effects on drugs metabolism, using microssomal fractions and High Performance Liquid Chromatography technique as an analytical tool. (AU)