TY - JOUR
T1 - The role of gut microbiota in the modulation of drug action: a focus on some clinically significant issues
AU - Curro', Diego
PY - 2018
Y1 - 2018
N2 - Introduction: A healthy gut microbiota is necessary for the normal operation of several body functions, including gastrointestinal sensitivity and motility, lipid and glucid metabolism, immune surveillance, and host behavior. In addition, intestinal bacteria contribute to determining the pharmacological properties of several drugs by producing different drug metabolizing enzymes. Areas covered: Four enzymatic processes are discussed: prodrug activation; drug inactivation; drug deconjugation; and hydrolysis of natural glycosides with further metabolism of released aglycones. For each of these processes, a literature search has been undertaken on certain paradigmatic examples that have significant clinical implications: aminosalicylates and anthranoid laxatives; digoxin; irinotecan and non-steroidal anti-inflammatory drugs (NSAIDs); rutin, diosmin, and baicalin. Expert commentary: The modulation of certain reactions catalyzed by gut bacterial enzymes may offer new opportunities to improve the clinical efficacy of drugs such as aminosalicylates, and natural glycosides by increasing their metabolic transformation, and of digoxin by reducing its inactivation, or to decrease the lower intestinal toxicity of irinotecan, and NSAIDs by inhibiting the hydrolytic cleavage of their conjugates. Randomized clinical trials are awaited to clarify whether new intervention strategies may modulate these processes and provide clinical benefits such as improved therapeutic outcomes and drug safety profiles.
AB - Introduction: A healthy gut microbiota is necessary for the normal operation of several body functions, including gastrointestinal sensitivity and motility, lipid and glucid metabolism, immune surveillance, and host behavior. In addition, intestinal bacteria contribute to determining the pharmacological properties of several drugs by producing different drug metabolizing enzymes. Areas covered: Four enzymatic processes are discussed: prodrug activation; drug inactivation; drug deconjugation; and hydrolysis of natural glycosides with further metabolism of released aglycones. For each of these processes, a literature search has been undertaken on certain paradigmatic examples that have significant clinical implications: aminosalicylates and anthranoid laxatives; digoxin; irinotecan and non-steroidal anti-inflammatory drugs (NSAIDs); rutin, diosmin, and baicalin. Expert commentary: The modulation of certain reactions catalyzed by gut bacterial enzymes may offer new opportunities to improve the clinical efficacy of drugs such as aminosalicylates, and natural glycosides by increasing their metabolic transformation, and of digoxin by reducing its inactivation, or to decrease the lower intestinal toxicity of irinotecan, and NSAIDs by inhibiting the hydrolytic cleavage of their conjugates. Randomized clinical trials are awaited to clarify whether new intervention strategies may modulate these processes and provide clinical benefits such as improved therapeutic outcomes and drug safety profiles.
KW - Animals
KW - Gastrointestinal Microbiome
KW - Gastrointestinal Tract
KW - Glycosides
KW - Gut microbiota
KW - Humans
KW - NSAIDs
KW - Pharmaceutical Preparations
KW - Pharmacology
KW - Pharmacology (medical)
KW - Prodrugs
KW - Randomized Controlled Trials as Topic
KW - Toxicology and Pharmaceutics (all)
KW - aminosalicylates
KW - baicalin
KW - digoxin
KW - drug metabolism
KW - irinotecan
KW - rutin
KW - Animals
KW - Gastrointestinal Microbiome
KW - Gastrointestinal Tract
KW - Glycosides
KW - Gut microbiota
KW - Humans
KW - NSAIDs
KW - Pharmaceutical Preparations
KW - Pharmacology
KW - Pharmacology (medical)
KW - Prodrugs
KW - Randomized Controlled Trials as Topic
KW - Toxicology and Pharmaceutics (all)
KW - aminosalicylates
KW - baicalin
KW - digoxin
KW - drug metabolism
KW - irinotecan
KW - rutin
UR - https://publicatt.unicatt.it/handle/10807/114813
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85041215749&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85041215749&origin=inward
U2 - 10.1080/17512433.2018.1414598
DO - 10.1080/17512433.2018.1414598
M3 - Article
SN - 1751-2433
VL - 11
SP - 171
EP - 183
JO - Expert Review of Clinical Pharmacology
JF - Expert Review of Clinical Pharmacology
IS - 2
ER -