title: Hepatobiliary excretion of tributylmethylamonium in rats with lipopolysaccharide-induced acute inflammation.
abstract: The alteration in the pharmacokinetic behaviors of organic cations (OCs) in rats during acute inflammation (Al) was investigated. Al was induced by an intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg) 24 hr prior to the start of pharmacokinetic studies. Tributylmethylammonium (TBuMA) was selected as a model OC since it is largely excreted into bile, and is neither metabolized nor binds to proteins in the body. When TBuMA was administered intravenously to Al rats at a dose of 6.6 micromole/kg, the AUC was increased, while biliary excretion (i.e., cumulative amount and apparent clearance) was decreased compared to normal rats. When TBuMA was administered intravenously to Al rats at a constant rate (i.e., a bolus injection at a dose of 1.5 micromole/kg followed by a constant infusion at a rate of 1.5 micromole/kg/hr for 165 min), steady-state concentrations of plasma and liver concentrations of TBuMA were increased significantly, while in vivo hepatic uptake (amount) and canalicular excretion (clearance) were decreased. These results are consistent with a hypothesis in which both the sinusoidal uptake of TBuMA into hepatocytes via the OCT1 and the canalicular excretion of the compound from hepatocytes via the P-gp are decreased by LPS-induced Al.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
authors.forename: In-Kyung
authors.initials: IK
authors.lastname: Lee
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Lee
authors.forename: Im-Sook
authors.initials: IS
authors.lastname: Song
authors.forename: Suk-Jae
authors.initials: SJ
authors.lastname: Chung
authors.forename: Sang-Geon
authors.initials: SG
authors.lastname: Kim
authors.forename: Myung-Gull
authors.initials: MG
authors.lastname: Lee
authors.forename: Chang-Koo
authors.initials: CK
authors.lastname: Shim
mesh_terms: D000208:Acute Disease; D000818:Animals; D001652:Bile Ducts / Q000187:drug effects / Q000378:metabolism*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008070:Lipopolysaccharides; D000644:Quaternary Ammonium Compounds; C043902:tri-n-butylmethylammonium