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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effects of hepatic fibrosis on ofloxacin pharmacokinetics in rats.

The purpose of the present work was to study the pharmacokinetics of ofloxacin, a poorly metabolised drug, in experimental hepatic fibrosis. The possible roles of small intestinal P-glycoprotein (P-gp) and cytochrome P450 (CYP) in the bioavailability of ofloxacin were also evaluated. Rat hepatic fibrosis model was successfully induced using complex factors including carbon tetrachloride, ethanol and high fat. After rats received a single oral or intravenous dose of ofloxacin (40 mg kg(-1)), the plasma concentrations of ofloxacin were monitored at the scheduled time using spectrofluorimetric assay. Plasma concentration-time profiles were comodeled using compartmental method. Meanwhile, microsomal CYP isoenzymatic levels and P-gp expression in small intestines were compared between normal and hepatic fibrosis rats. When ofloxacin was administered intravenously, C(max) and the distribution half-life increased significantly in comparison with normal group, whereas the distribution rate constants, the apparent volume of distribution decreased. Oral ofloxacin bioavailability was significantly altered in hepatic fibrosis rats. AUC and C(max) were reduced, while the absorption half-life, peak time and elimination half-life significantly were prolonged, suggesting that both the extent and the rate of ofloxacin absorption were decreased. Furthermore, the increases in the levels of microsomal ethoxyresorufin O-deethylase and erythromycin N-demethylase were accompanied with up-regulation of mdr 1a mRNA in the small intestines of hepatic fibrosis rats when compared to those of the normal rats. The Results showed that pharmacokinetics of ofloxacin could be altered in hepatic fibrosis. Up-regulated P-gp expression and increased CYP isoenzymatic activities of small intestines in hepatic fibrosis rats may contribute to the decreased bioavailability and increased elimination of ofloxacin after oral administration.[1]


  1. Effects of hepatic fibrosis on ofloxacin pharmacokinetics in rats. Wang, H., Liao, Z.X., Chen, M., Hu, X.L. Pharmacol. Res. (2006) [Pubmed]
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