The pharmacokinetics of irinotecan in rats with immunological liver injury / 中国药学杂志
Chinese Pharmaceutical Journal
; (24): 1233-1236, 2012.
Article
in Zh
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| ID: wpr-860663
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ABSTRACT
OBJECTIVE: To investigate the pharmacokinetics of irinotecan (CPT-11) in SD rats with immunological liver injury. METHODS: The animal model of immunological liver injury was established by intraperitoneal injection of lipopolysaccharide (LPS) plus Bacille-Calmette-Guerin (BCG) in rats. Rats were randomly divided into two groups; normal control group and immunological liver injury model group. The two groups were injected with CPT-11 (20 mg · kg-1) via tail vein and plasma concentrations of CPT-11 and its metabolite SN-38 were determined by HPLC. Pharmacokinetical parameters were calculated. RESULTS: Compared with the normal control group, AUC0-24h, AUC0-∞ and ρmax of CPT-11 in immunological liver injury rats were increased significantly (P < 0.05), but AUC0-24h, AUC0-∞ and ρmax of SN-38 were decreased significantly (P < 0.05). CONCLUSION: Under the state of immunological liver injury, the hydrolysis of CPT-11 is inhibited significantly. The underlying mechanism may be related to the down-regulation of the expression of carboxylesterase 2 by LPS. Copyright 2012 by the Chinese Pharmaceutical Association.
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Zh
Journal:
Chinese Pharmaceutical Journal
Year:
2012
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Article