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Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal ß-glucuronidase activity.
Zhong, Ze-Yu; Sun, Bin-Bin; Shu, Nan; Xie, Qiu-Shi; Tang, Xian-Ge; Ling, Zhao-Li; Wang, Fan; Zhao, Kai-Jing; Xu, Ping; Zhang, Mian; Li, Ying; Chen, Yang; Liu, Li; Xia, Lun-Zhu; Liu, Xiao-Dong.
Afiliación
  • Zhong ZY; Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
  • Sun BB; Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
  • Shu N; Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
  • Xie QS; Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
  • Tang XG; Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
  • Ling ZL; Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
  • Wang F; Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
  • Zhao KJ; Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
  • Xu P; Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
  • Zhang M; Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
  • Li Y; Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
  • Chen Y; Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
  • Liu L; Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
  • Xia LZ; The First Affiliated Hospital, Anhui University of Chinese Medicine, Hefei 230031, China.
  • Liu XD; Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
Acta Pharmacol Sin ; 37(7): 1002-12, 2016 Jul.
Article en En | MEDLINE | ID: mdl-27180979
ABSTRACT

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. ß-Glucuronidase activity in intestinal content, bovine liver and E coli 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, ß-glucuronidase activity in small intestinal content was region-dependent proximal intestineintestineAdministration of ciprofloxac caused significant reduction of ß-glucuronidase activity in distal small intestine, and particularly in ileal valve. Furthermore, ciprofloxacin (10-2000 µmol/L) dose-dependently inhibited ß-glucuronidase activity in distal small intestine content or E coli 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 ß-glucuronidase activity.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Ciprofloxacina / Antiinflamatorios no Esteroideos / Diclofenaco / Circulación Enterohepática / Glucuronidasa / Enfermedades Intestinales / Intestino Delgado Límite: Animals Idioma: En Revista: Acta Pharmacol Sin Asunto de la revista: FARMACOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Ciprofloxacina / Antiinflamatorios no Esteroideos / Diclofenaco / Circulación Enterohepática / Glucuronidasa / Enfermedades Intestinales / Intestino Delgado Límite: Animals Idioma: En Revista: Acta Pharmacol Sin Asunto de la revista: FARMACOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: China