Dose-dependent pharmacokinetics of telithromycin after intravenous and oral administration to rats: Contribution of intestinal first-pass effect to low bioavailability

Purpose. To evaluate the pharmacokinetics of telithromycin after intravenous and oral administration and to find the reason for incomplete F value ( first pass-effect) after intravenous, intraportal, intragastric, and intraduodenal administration to rats. Methods. Telithromycin was administered intravenously or orally at doses of 20, 50, and 100 mg/kg to rats. And hepatic, gastric, and intestinal first-pass effects of telithromycin were also measured after intravenous, intraportal, intragastric, and intraduodenal administration at a dose of 50 mg/kg to rats. Results. The dose-normalized AUC values of telithromycin were dose-dependent ( increased with increasing doses) after both intravenous and oral dose ranges studied, possibly due to saturable metabolism of telithromycin. After oral administration ( 50 mg/kg), approximately 4.06% of oral dose was not absorbed, F was approximately 27.5%, and the intestinal first-pass effect was approximately 63.4% of oral dose. The first-pass effects of telithromycin in the lung, heart, stomach, and liver were almost negligible, if any, in rats. Conclusions. The low F of telithromycin at a dose of 50 mg/kg was mainly due to considerable intestinal first-pass effect, approximately 63.4% of oral dose, in rats.