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P-glycoprotein (P-gp) expression determines the absorption, distribution, metabolism and excretion of many drugs in the body. Also, up-regulation of P-gp acts as a defense mechanism against acute inflammation. This study examined expression levels of  abcb1  mRNA and localization of P-gp protein in the liver, kidney, duodenum, jejunum and ileum in healthy and  E. coli  infected broilers by real time RT-PCR and immunohistochemistry. Meanwhile, pharmacokinetics of orally administered enrofloxacin was also investigated in healthy and infected broilers by HPLC. The results indicated that  E. coli  infection up-regulated expression of  abcb1  mRNA levels significantly in the kidney, jejunum and ileum ( P <0.05), but not significantly in the liver and duodenum ( P >0.05). However, the expression level of  CYP 3A37  mRNA were observed significantly decreased only in liver and kidney of  E. coli  infected broilers ( P <0.05) compared with healthy birds. Furthermore, the infection reduced absorption of orally administered enrofloxacin, significantly decreased C max  (0.34 vs 0.98 µg mL −1 ,  P  = 0.000) and AUC 0-12h  (4.37 vs 8.88 µg mL −1  h,  P  = 0.042) of enrofloxacin, but increased T max  (8.32 vs 3.28 h,  P  = 0.040), T 1/2a (2.66 vs 1.64 h −1 ,  P  = 0.050) and V/F (26.7 vs 5.2 L,  P  = 0.040). Treatment with verapamil, an inhibitor of P-gp, significantly improved the absorption of enrofloxacin in both healthy and infected broilers. The results suggest that the  E. coli  infection induces intestine P-gp expression, altering the absorption of orally administered enrofloxacin in broilers.

plos one

E. coli Infection Modulates the Pharmacokinetics of Oral Enrofloxacin by Targeting P-Glycoprotein in Small Intestine and CYP450 3A in Liver and Kidney of Broilers