TY - JOUR
T1 - The Use of Tissue Concentrations of Biological and Small-Molecule Therapies in Clinical Studies of Inflammatory Bowel Diseases
AU - Bayoumy, Ahmed B.
AU - Derijks, Luc J.J.
AU - Oldenburg, Bas
AU - de Boer, Nanne K.H.
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/12
Y1 - 2024/12
N2 - Abstract: The introduction of biological therapies has revolutionized inflammatory bowel disease (IBD) management. A critical consideration in developing these therapies is ensuring adequate drug concentrations at the site of action. While blood-based biomarkers have shown limited utility in optimizing treatment (except for TNF-alpha inhibitors and thiopurines), tissue drug concentrations may offer valuable insights. In antimicrobial therapies, tissue concentration monitoring is standard practice and could provide a new avenue for understanding the pharmacokinetics of biological and small-molecule therapies in IBD. Various methods exist for measuring tissue concentrations, including whole tissue sampling, MALDI-MSI, microdialysis, and fluorescent labeling. These techniques offer unique advantages, such as spatial drug-distribution mapping, continuous sampling, or cellular-level analysis. However, challenges remain, including sampling invasiveness, heterogeneity in tissue compartments, and a lack of standardized bioanalytical guidelines. Drug pharmacokinetics are influenced by multiple factors, including molecular properties, disease-induced changes in the gastrointestinal tract, and the timing of sample collection. For example, drug permeability, solubility, and interaction with transporters may vary between Crohn’s disease and ulcerative colitis. Research into the tissue concentrations of drugs like anti-TNF agents, ustekinumab, vedolizumab, and tofacitinib has shown variable correlations with clinical outcomes, suggesting potential roles for tissue concentration monitoring in therapeutic drug management. Although routine clinical application is not yet established, exploring tissue drug concentrations may enhance understanding of IBD pharmacotherapy.
AB - Abstract: The introduction of biological therapies has revolutionized inflammatory bowel disease (IBD) management. A critical consideration in developing these therapies is ensuring adequate drug concentrations at the site of action. While blood-based biomarkers have shown limited utility in optimizing treatment (except for TNF-alpha inhibitors and thiopurines), tissue drug concentrations may offer valuable insights. In antimicrobial therapies, tissue concentration monitoring is standard practice and could provide a new avenue for understanding the pharmacokinetics of biological and small-molecule therapies in IBD. Various methods exist for measuring tissue concentrations, including whole tissue sampling, MALDI-MSI, microdialysis, and fluorescent labeling. These techniques offer unique advantages, such as spatial drug-distribution mapping, continuous sampling, or cellular-level analysis. However, challenges remain, including sampling invasiveness, heterogeneity in tissue compartments, and a lack of standardized bioanalytical guidelines. Drug pharmacokinetics are influenced by multiple factors, including molecular properties, disease-induced changes in the gastrointestinal tract, and the timing of sample collection. For example, drug permeability, solubility, and interaction with transporters may vary between Crohn’s disease and ulcerative colitis. Research into the tissue concentrations of drugs like anti-TNF agents, ustekinumab, vedolizumab, and tofacitinib has shown variable correlations with clinical outcomes, suggesting potential roles for tissue concentration monitoring in therapeutic drug management. Although routine clinical application is not yet established, exploring tissue drug concentrations may enhance understanding of IBD pharmacotherapy.
KW - inflammatory bowel disease
KW - infliximab
KW - methotrexate
KW - tissue concentrations
KW - tofacitinib
KW - ustekinumab
KW - vedolizumab
UR - http://www.scopus.com/inward/record.url?scp=85213367022&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics16121497
DO - 10.3390/pharmaceutics16121497
M3 - Review article
AN - SCOPUS:85213367022
SN - 1999-4923
VL - 16
JO - Pharmaceutics
JF - Pharmaceutics
IS - 12
M1 - 1497
ER -