Pharmacological, Pharmacokinetic, and Pharmacogenomic Aspects of Disorders of Gut-Brain Interaction.

Abstract

We conducted a literature review of preclinical, animal and human pharmacology, pharmacokinetics, and pharmacogenomics related to disorders of gut-brain interaction (DGBI). This article reviews animal models of visceral pain, abnormal motility, and epithelial transport, and human models of motility and sensation and their utility in drug development for DGBI with focus on colorectal and gastric biomarkers. We highlight preclinical studies related to pharmacology, pharmacokinetics, and toxicology required for development of novel therapeutic agents, and principles of pharmacogenomics based on drug metabolism and the few examples of pharmacogenetics related to targets in treatment of IBS. Finally, we summarize the human pharmacology of medications used for treatment of DGBI based on the individual indications - specifically psychopharmacologic and nonpsychotropic agents for DGBI associated with dyspepsia, constipation, diarrhea, and visceral pain, as well as introduction of biomarkers for individualizing therapy for IBS and recommendations for future research.