ArticleToxicology and applied pharmacology2020
Irinotecan-mediated diarrhea is mainly correlated with intestinal exposure to SN-38: Critical role of gut Ugt.
Article in Toxicology and applied pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 42 citations in OpenAlex.
- Microbiome-Shaped Metastatic Niches in Colorectal Cancer: Organ-Specific Patterns, Immune-Metabolic Mechanisms, and Therapeutic Translation.Microorganisms · 2026Review
- Microbiome-Modulating Strategies in Anticancer Therapy: A Review of Current Evidence and Recommendations for Further Treatment Improvement.Probiotics and antimicrobial proteins · 2026Review
- Development of an adult whole-body PBPK model of irinotecan and its metabolites for predicting UGT1A1/CYP3A-mediated drug-drug interactions.Frontiers in pharmacology · 2026Article
- OATP2B1 Deficiency Ameliorates Irinotecan-Induced Gastrointestinal Toxicity.Clinical and translational science · 2026Article
- Hypericin and hyperforin from St. John's Wort are potent intestinal UGT inhibitors with distinct binding modes: mechanistic and quantitative prediction of clinical drug-drug interaction risk.Frontiers in pharmacology · 2026Article
- Butyrate prevents chemotherapy-induced gastrointestinal toxicity and microbial dysbiosis.Scientific reports · 2025Article
- Butyrate Modulates Intestinal Microbiome and Epithelial Function to Attenuate Irinotecan-induced GI Toxicity.Research square · 2025Article
- The role of the gut microbiota in chemotherapy response, efficacy and toxicity: a systematic review.NPJ precision oncology · 2025Article
- Microalgae-carrying nanomedicine for bioadhesive drug delivery for treating chemotherapy-induced intestinal injury.Asian journal of pharmaceutical sciences · 2025Article
- Toxicities and management strategies of emerging antibody-drug conjugates in breast cancer.Therapeutic advances in medical oncology · 2025Review
- Targeted inhibition of Gus-expressingActa pharmaceutica Sinica. B · 2024Article
- Fecal SN-38 Content as a Surrogate Predictor of Intestinal SN-38 Exposure and Associated Irinotecan-induced Severe Delayed-Onset Diarrhea by a Novel Use of the Spectrofluorimetric Method.Pharmaceutical research · 2024Article
- Fecal microbiota transplantation: current challenges and future landscapes.Clinical microbiology reviews · 2024Review
- Optimized rat models better mimic patients with irinotecan-induced severe diarrhea.Toxicology mechanisms and methods · 2024Article
- The role of gut microbial β-glucuronidase in drug disposition and development.Drug discovery today · 2022Review
- α-Glucosidase and Bacterial β-Glucuronidase Inhibitors from the Stems ofPharmaceuticals (Basel, Switzerland) · 2022Article
- Chemotherapy induced gastrointestinal toxicities.Advances in cancer research · 2022Review
- Potential role of drug metabolizing enzymes in chemotherapy-induced gastrointestinal toxicity and hepatotoxicity.Expert opinion on drug metabolism & toxicology · 2020Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
background and purposeIrinotecan-induced diarrhea (IID) results from intestinal damages by its active metabolite SN-38. Alleviation of these damages has focused on lowering luminal SN-38 concentrations. However, it is unclear if the enteric bioavailability of SN-38 is mostly dependent on luminal SN-38 concentrations. EXPERIMENTAL APPROACH: Irinotecan (50 mg/kg, i.p. once daily for 6 days) was administered to female wildtype FVB, Mdr1a (-/-), Mrp2 (-/-) and Bcrp1 (-/-) mice for pharmacokinetic (PK), toxicokinetic (TK) and biodistribution studies. Plasma PK/TK profiles and tissues drug distribution were determined after first or sixth daily doses, along with activities of blood and gut esterases and intestinal Ugts. Caco-2 cells and bile-cannulate mice were used to further investigate intestinal and biliary disposition of irinotecan and its metabolites. KEY
resultsSignificant differences in IID severity were observed with the susceptible rank of Bcrp1(-/-) > wildtype FVB > Mdr1a(-/-) > Mrp2(-/-). This rank order did not correlate with biliary excretion rates of SN-38/SN-38G. Rather, the severity was best correlated (R = 0.805) with the intestinal ratio of C CONCLUSION AND IMPLICATIONS: Intestinal SN-38 exposure is mainly affected by intestinal Ugt activities and blood esterase activities, and strongly correlated with severity of IID. Modulating intestinal SN-38 concentration and gut Ugt expression should be the focus of future studies to alleviate IID.
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