Bioavailability is the most important factor for the efficacy of any drug and it is determined by P- glycoprotein (P-gp)\r\nexpression. Confirmation of P-gp expression during ontogeny is needed for understanding the differences in\r\ntherapeutic efficacy of any drug in juvenile and adult animals. In this study, Abcb1 mRNA levels in the liver and\r\nintestine of broilers during ontogeny were analysed by RT qPCR. Cellular distribution of P-gp was detected by\r\nimmunohistochemstry. Age-related differences of enrofloxacin pharmacokinetics were also studied. It was found that\r\nbroilers aged 4 week-old expressed significantly (P<0.01) higher levels of P-gp mRNA in the liver, jejunum and ileum,\r\nthan at other ages. However, there was no significant (P>0.05) age-related difference in the duodenum. Furthermore,\r\nthe highest and lowest levels of Abcb1 mRNA expression were observed in the jejunum, and duodenum,\r\nrespectively. P-gp immunoreactivity was detected on the apical surface of the enterocytes and in the bile canalicular\r\nmembranes of the hepatocytes. Pharmacokinetic analysis revealed that the 8 week-old broilers, when orally\r\nadministrated enrofloxacin, exhibited significantly higher Cmax (1.97 vs. 0.98 �µgâ�¢ml-1, P=0.009), AUC(14.54 vs. 9.35\r\n�µgâ�¢ml-1â�¢h, P=0.005) and Ka (1.38 vs. 0.43 h-1, P=0.032), as well as lower Tpeak (1.78 vs. 3.28 h, P=0.048) and T1/2ka\r\n(0.6 vs. 1.64 h, P=0.012) than the 4 week-old broilers. The bioavailability of enrofloxacin in 8 week-old broilers was\r\nincreased by 15.9%, compared with that in 4 week-old birds. Interestingly, combining verapamil, a P-gp modulator,\r\nsignificantly improved pharmacokinetic behaviour of enrofloxacin in all birds. The results indicate juvenile broilers had\r\na higher expression of P-gp in the intestine, affecting the pharmacokinetics and reducing the bioavailability of oral\r\nenrofloxacin in broilers. On the basis of our results, it is recommended that alternative dose regimes are necessary\r\nfor different ages of broilers for effective therapy.
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