Beyond Traditional Pharmacokinetics: The Expanding Influence of Microbiota, Bile Acids, and Other Modulators on Drug Metabolism and Transport

Classically, the study of pharmacokinetics (PK) has centered on hepatic metabolism and renal excretion as the primary determinants of drug exposure. However, the landscape of drug metabolism and transport is shifting. It is becoming increasingly clear that "non-traditional" modulators, specifically the gut microbiota and the complex signaling network of bile acids, play a critical, yet often underestimated, role in determining the efficacy and safety of pharmaceutical agents.The interplay between the host and the microbiome (the "second genome") introduces significant inter-individual variability in drug response. Bacterial enzymes can directly metabolize drugs, alter their bioavailability, or reactivate excreted metabolites, leading to toxicity. Simultaneously, bile acids act not only as facilitators of lipid absorption but as potent signaling molecules regulating drug transporters and metabolic enzymes via nuclear receptors (such as FXR and PXR).This Research Topic aims to explore these expanding frontiers of pharmacokinetics. We seek to characterize how these modulators influence Absorption, Distribution, Metabolism, and Excretion (ADME) and to integrate this knowledge into modern drug development and clinical practice.We welcome data covering, but not limited to, the following themes:- The Microbiome Factor: Mechanisms of direct drug metabolism by gut bacteria and the impact of dysbiosis on PK profiles.- Bile Acids as Regulators: The role of bile acids in modulating drug transporters (e.g., P-gp, OATPs) and metabolic enzymes.- Microbial Ligands and Detoxification Pathways: The impact of microbe-derived nuclear receptor and AhR ligands (e.g., mimicry compounds, acetylated bile acids) and the specific mechanisms of LCA detoxification.- Novel Excipients & Permeation Enhancers: The influence of formulation strategies on membrane transport and biological barriers.- Clinical & Industry Implications: Translating these findings into PBPK modeling, dose adjustment strategies, and regulatory considerations in drug development.- Food-Drug and Disease-Drug Interactions: How diet or metabolic disorders alter the microbiota-bile acid axis to impact pharmacokinetics. Topic editors: Maja Ðanic, Charles Oo, Momir Mikov, Bojan Stanimirov Source: https://www.frontiersin.org/research-topics/77563/beyond-traditional-pharmacokinetics-the-expanding-influence-of-microbiota-bile-acids-and-other-modulators-on-drug-metabolism-and-transport