Lipopolysaccharide upregulating P-glycoprotein in small intestine alters pharmacokinetics of orally administered enrofloxacin in broilers

Lipopolysaccharide (lps) modulates p-glycoprotein (p-gp) expression alters pharmacokinetics of its substrates in rodents. however,its influence on p-gp expression in chickens still poorly characterized. this study evaluated lps effects on p-gp expression in liver,small intestine and kidney by immunohistochemistry and pharmacokinetics of enrofloxacin in lps-treated and non-treated broilers. the highest immunoreactivity of p-gp was found in the apical membrane of enterocytes,proximal tubules of kidney and biliary canalicular membranes of hepatocytes at 2 to 6 h after lps administration. the oral enrofloxacin significantly decreased auc0-∞ (lps: 19.27±0.65 vs control: 23.64±1.27 μg•ml-1•h-1,p < 0.05),cmax (lps: 0.83±0.07 vs control: 1.57±0.11 μg•ml-1,p<0.01) and ka (lps: 0.24±0.10 vs control: 1.67±0.11 h-1,p < 0.05),and increased tmax (lps: 7.79±1.29 vs control: 1.94±0.10 h,p < 0.05) and t1/2a (lps: 4.03±1.02 vs control: 0.41±0.03 h,p < 0.05) in lps-treated broilers as compared to control. verapamil significantly attenuated lps effects on the pharmacokinetics of oral enrofloxacin. however,iv enrofloxacin didn't show significant changes in key parameters among three groups. the results implied that lps reduced auc0-∞ of oral enrofloxacin through up-regulating p-gp in small intestine. this study suggests that dosages should be adjusted initially to achieve therapeutic concentration at the site of action during lps infection in broilers. © 2017 pvj.