Pharmacokinetics and bioavailability enhancement of natural products

Abstract

Many natural products show promising activities in in vitro studies and preclinical in vivo studies, including cancer chemoprevention agents. However, results of human clinical trials with some of these natural products often vary. One of the major reasons for the unsuccessful translation of in vitro and animal studies to human studies is the poor bioavailability associated with natural products. Recent research has progressed much in the way of isolating individual active natural products and investigating their potential, leading to exciting treatment possibilities. The continued characterization of the mechanisms of their pharmacokinetic dispositions yields helpful information about issues that need to be managed to realize successful clinical utility. This chapter gives an introduction to the pharmacokinetics of six selected natural product chemopreventive agents.We discuss their absorption, distribution, metabolism, and elimination (ADME), based on in vitro and in vivo experimental models. Next, we discuss approaches to improve oral bioavailability of natural compounds. A few of the novel approaches undertaken to make formulations of natural compounds with improved pharmacokinetic profiles and higher oral bioavailability are described. Finally, we present select natural compounds which have been or may be used as bioavailability enhancers in in vivo studies. Some mechanisms for bioenhancement include inhibition of metabolic enzymes (enzyme inhibition) and inhibition of the transporters involved in the elimination of molecules. Natural products have a wide range of promising biological effects, but their pharmacokinetic properties need to be understood in order to better address biopharmaceutical challenges. Addressing these challenges will allow us to better explore the pharmacological potential of these compounds, either as single agents or in bioenhancing combinations.