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.

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. 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. 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. 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.

Zheng Z ，Šaponjac VT ，Singh R ，Chen J ，Srinual S ，Yin T ，Sun R ，Hu M ... -  《-》

Streptomycin alleviates irinotecan-induced delayed-onset diarrhea in rats by a mechanism other than inhibition of β-glucuronidase activity in intestinal lumen.

Kurita A ，Kado S ，Matsumoto T ，Asakawa N ，Kaneda N ，Kato I ，Uchida K ，Onoue M ，Yokokura T ... -  《-》

Modified irinotecan hydrochloride (CPT-11) administration schedule improves induction of delayed-onset diarrhea in rats.

Kurita A ，Kado S ，Kaneda N ，Onoue M ，Hashimoto S ，Yokokura T ... -  《CANCER CHEMOTHERAPY AND PHARMACOLOGY》

Relationship between the pharmacokinetics of irinotecan and diarrhea during combination chemotherapy with cisplatin.

Kudoh S ，Fukuoka M ，Masuda N ，Yoshikawa A ，Kusunoki Y ，Matsui K ，Negoro S ，Takifuji N ，Nakagawa K ，Hirashima T ... -  《-》

Intestinal alkalization as a possible preventive mechanism in irinotecan (CPT-11)-induced diarrhea.

Ikegami T ，Ha L ，Arimori K ，Latham P ，Kobayashi K ，Ceryak S ，Matsuzaki Y ，Bouscarel B ... -  《CANCER RESEARCH》