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.

Autor: Zheng Z; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Houston, TX, 77204, USA., Šaponjac VT; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Houston, TX, 77204, USA.; Sanarentero LLC, 514 N. Elder Grove Dr., Pearland, TX, 77584, USA.; Faculty of Technology, University of Novi Sad, Bulevar Cara Lazara 1, 21000, Novi Sad, Serbia., Singh R; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Houston, TX, 77204, USA.; Sanarentero LLC, 514 N. Elder Grove Dr., Pearland, TX, 77584, USA., Chen J; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Houston, TX, 77204, USA., Srinual S; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Houston, TX, 77204, USA., Yin T; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Houston, TX, 77204, USA., Sun R; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Houston, TX, 77204, USA. rsun5@central.uh.edu., Hu M; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Houston, TX, 77204, USA. mhu4@central.uh.edu.; Sanarentero LLC, 514 N. Elder Grove Dr., Pearland, TX, 77584, USA. mhu4@central.uh.edu.
Jazyk: angličtina
Zdroj: Pharmaceutical research [Pharm Res] 2024 Sep; Vol. 41 (9), pp. 1855-1867. Date of Electronic Publication: 2024 Aug 13.
DOI: 10.1007/s11095-024-03755-6
Abstrakt: Background: Irinotecan administration can lead to severe delayed-onset diarrhea (SDOD) in clinical practice. Currently, there is no reliable surrogate predictor of intestinal exposure to SN-38 and subsequent diarrhea incidence.
Methods: The relationship between fecal 7-ethyl-10-hydroxycamptothecin (SN-38) content and SDOD was investigated in Fisher 344 rats using a novel spectrofluorimetric method. Additionally, a pharmacokinetic study of irinotecan was performed to evaluate the biodistribution of SN-38 to establish the relationship between tissue and fecal SN-38 exposure.
Results: The spectrofluorimetric method was successfully employed to measure fecal SN-38 and CPT-11 content from Day 3 to Day 6 post-irinotecan administration. Only fecal SN-38 content on Day 3 exhibited a significantly positive correlation with SDOD incidence on Days 4 and 5. A cutoff value of SN-38 ≥ 0.066 mg/g in feces was identified, predicting severe diarrhea incidence with 81% accuracy and 80% specificity. The positive correlation between fecal SN-38 content and SN-38 exposure in the ileum on Day 3 was also reflected in the changes of indicators during intestinal injury, such as prostaglandin E2 level and antioxidant activity.
Conclusion: Fecal SN-38 content proves to be representative of intestinal exposure to SN-38, indicative of intestinal injury, and predictive of SDOD incidence in rats, while the spectrofluorimetric method demonstrates the translational potential.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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