Dose-dependent pharmacokinetics of telithromycin after intravenous and oral administration to rats: contribution of intestinal first-pass effect to low bioavailability.
OBJECTIVE
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.
Lee
Joo Hyun
JH
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
Lee
Myung Gull
MG
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism*; D048628:Ketolides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism
D000900:Anti-Bacterial Agents; D048628:Ketolides; D012709:Serum Albumin; C106791:telithromycin