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 ofkidney 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.