title: Effect of hesperidin on the pharmacokinetics of CPT-11 and its active metabolite SN-38 by regulating hepatic Mrp2 in rats.
abstract: The usage of irinotecan hydrochloride (CPT-11) chemotherapy is hindered by its dose-limiting diarrhea which appears to be associated with the intestinal exposure to SN-38, the active metabolite of CPT-11. Hesperidin, a safe and natural food ingredient flavonoid, exhibits various biological properties. Accumulated evidence showed that the regulatory effect of hesperidin on the expression of Mrp2 in the liver may be one of the critical factors controlling the biliary excretion of SN-38. This study examined the effect of hesperidin on the pharmacokinetics of CPT-11 and SN-38 as well as the regulatory effect on the hepatic expression of Mrp2. Compared with the control group, the AUC5-twas increased to 115% of CPT-11 and 122% of SN-38; the CL was decreased to 87% for CPT-11; the tissue concentration was increased in the liver, kidney and colon; and the accumulated biliary excretion was significantly decreased to 77% for CPT-11 and 76% for SN-38 in hesperidin-treated rats. Furthermore, the expression of Mrp2 in the liver was significantly decreased to 37% in the hesperidin-treated rats compared with that of the control group. These results indicate that oral administration of hesperidin significantly increased the AUC5-tand reduced the clearance of CPT-11 and SN-38, possibly by decreasing the hepatic expression of Mrp2, and thus inhibiting the biliary excretion of CPT-11 and SN-38. The results from this present study suggest that hesperidin may reduce the exposure of CPT-11 and SN-38 in the intestine by reducing the amount of biliary excretion of CPT-11 and SN-38. Copyright © 2016 John Wiley & Sons, Ltd.
authors: Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou, 730000, PR China.|College of Pharmaceutical Sience, Lanzhou University, Lanzhou, 730000, PR China.
authors: Xingdong
authors: X
authors: Wang
authors: Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou, 730000, PR China.
authors: Zhi
authors: Z
authors: Rao
authors: Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou, 730000, PR China.
authors: Hongyan
authors: H
authors: Qin
authors: Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou, 730000, PR China.|College of Pharmaceutical Sience, Lanzhou University, Lanzhou, 730000, PR China.
authors: Guoqiang
authors: G
authors: Zhang
authors: Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou, 730000, PR China.
authors: Yanrong
authors: Y
authors: Ma
authors: College of Pharmaceutical Sience, Lanzhou University, Lanzhou, 730000, PR China.
authors: Yongwen
authors: Y
authors: Jin
authors: College of Pharmaceutical Sience, Lanzhou University, Lanzhou, 730000, PR China.
authors: Miao
authors: M
authors: Han
authors: College of Pharmaceutical Sience, Lanzhou University, Lanzhou, 730000, PR China.
authors: Axi
authors: A
authors: Shi
authors: Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou, 730000, PR China.
authors: Yanping
authors: Y
authors: Wang
authors: Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou, 730000, PR China. xinanwu6511@163.com.
authors: Xinan
authors: X
authors: Wu
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D006569:Hesperidin / Q000494:pharmacology*; D000077146:Irinotecan; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017208:Rats, Wistar
chemical_list: D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D006569:Hesperidin; D002166:Camptothecin
keywords: Mrp2; SN-38; hesperidin; irinotecan hydrochloride; pharmacokinetics