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Effect of X‐ray irradiation on pharmacokinetics of irinotecan hydrochloride and expression of CES 1 and CYP 3A1 in rats
Author(s) -
Yijie Qiao,
Xuejun Wang,
Yuanyao Xin,
Yongqiong Nian,
Jianxin Yang,
Yabin Duan,
Xiangyang Li
Publication year - 2019
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12456
Subject(s) - pharmacokinetics , irinotecan , irradiation , pharmacology , chemistry , messenger rna , medicine , cancer , biochemistry , colorectal cancer , physics , nuclear physics , gene
Concurrent chemoradiation with irinotecan hydrochloride ( CPT ‐11) is accepted for cancer treatment. However, the effects of X‐ray irradiation on chemotherapeutics in the plasma remain unclear. We evaluated the pharmacokinetics of CPT ‐11 in rats after exposure to X‐ray irradiation and examined the changes of protein and mRNA expression of CES 1 and CYP 3A1. The X‐ray irradiation with 1 Gy and 5 Gy was delivered to the whole body of rats. CPT ‐11 at 30 and 60 mg/kg, respectively, was intravenously infused 24 h after irradiation. CPT ‐11 was determined by RP ‐ HPLC in plasma. ELISA and PCR were used to analyze the protein and mRNA expression of CES 1 and CYP 3A1, respectively. Compared with control rats, the X‐ray irradiation decreased the AUC of CPT ‐11 (30 mg/kg) by 15.6% at 1 Gy and 39.0% at 5 Gy and increased the CL by 60.0% at 5 Gy. The X‐ray irradiation could also decrease the AUC of CPT ‐11 (60 mg/kg) and increase the CL . In addition, the protein and mRNA expression of CES 1 and CYP 3A1 were increased significantly in rats after irradiation. This study found significant changes in the pharmacokinetics of CPT ‐11 in rats after exposure to X‐ray irradiation, and they might be due to significant increases in the expressions of CYP 3A1 and CES 1. The pharmacokinetics of CPT ‐11 should be rechecked, and the optimal CPT ‐11 dose should be reevaluated during concurrent chemoradiation therapy.