RESUMEN
The study of the ADME features of the huge number of new chemical entities (NCEs) produced mainly by combinatorial chemistry has become a bottleneck in the drug development process. In response the pharmaceutical industry is involved in the development of new medium/high-throughput screening capabilities. The aim of this paper is to review some of the available in vitro ADME systems adapted to screening requirements together with the technological approaches which can be linked to medium/high-throughput molecular screening.
Asunto(s)
Técnicas Químicas Combinatorias , Evaluación Preclínica de Medicamentos/métodos , Farmacocinética , Animales , Células Cultivadas , HumanosRESUMEN
The extract of the fern Polypodium leucotomos (PL, Fernblock) is an oral photoprotectant with strong antioxidative properties. Recent studies to determine its chemical composition have shown 4-hydroxycinnamic acid (p-coumaric), 3 methoxy-4-hydroxycinnamic acid (ferulic), 3,4-dihydroxycinnamic acid (caffeic), 3-methoxy-4-hydroxybenzoic acid (vanillic) and 3-caffeoilquinic acid (chlorogenic) to be among its major phenolic components. No conclusive data are available, however, on the H2O2-scavenging capacity of these compounds, or on their absorption and metabolism following their oral intake. In the present work, their antioxidative capacity was assessed by the luminol/H2O2 assay, their absorption studied using Caco-2 cells to resemble the intestinal barrier, and their metabolism investigated using cultured primary rat hepatocytes. The antioxidant capacity of PL components increased in a concentration-dependent manner, with ferulic and caffeic acids the most powerful antioxidants. The apparent permeability results correspond to a human post-oral administration absorption of 70-100% for all tested substances. Coumaric, ferulic and vanillic acids were metabolized by CYP450-dependent mono-oxygenases and partially conjugated to glucuronic acid and sulfate. These phenolic compounds may contribute to the health benefits afforded by this oral photoprotectant.