Details

Autor(en) / Beteiligte

• Ze-yu ZHONG Bin-bin SUN Nan SHU Qiu-shi XIE Xiange TANG Zhao-li LING Fan WANG Kai-jing ZHAO Ping XU Mian ZHANG Ying LI Yang CHEN Li LIU Lun-zhu XIA Xiao-dong LIU

Titel

Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal 13-glucuronidase activity

Ist Teil von

• 中国药理学报：英文版, 2016 (7), p.1002-1012

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Aim： Diclofenac is a non-steroidal anti-inflammatory drug （NSAID）, which may cause serious intestinal adverse reactions （enteropathy）. In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac- induced enteropathy in rats. Methods： The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac （10 mg/kg, ig, or 5 mg/kg, iv）, with or without ciprofloxacin （20 mg/kg, ig） co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. β-Glucuronidase activity in intestinal content, bovine liver and E coil was evaluated. Results： Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, β-glucuronidase activity in small intestinal content was region-dependent： proximal intestine〈distal intestine〈ileal valve. Administration of ciprofloxac caused significant reduction of β-glucuronidase activity in distal small intestine, and particularly in ileal valve. Furthermore, ciprofloxacin （10-2000 pmol/L） dose-dependently inhibited β-glucuronidase activity in distal small intestine content or E coil incubated in vitro, but did not affect that in proximal small intestine content or bovine liver incubated in vitro. After receiving 6 oral doses or 15 intravenous doses of diclofenac, typical enteropathy was developed with severe enteropathy occurred in distal small intestine. Co-administration of ciprofloxacin significantly alleviated diclofenac-induced enteropathy. Conclusion： Co-administration of ciprofloxacin attenuated enterohepatic circulation of diclofenac and alleviated diclofenac-induced enteropathy in rats, partly via the inhibition of intestinal β-glucuronidase activity.