Hepatobiliary excretion of tributylmethylamonium in rats with lipopolysaccharide-induced acute inflammation.
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| 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.
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| Authors | In-Kyung Lee, Young-Mi Lee, Im-Sook Song, Suk-Jae Chung, Sang-Geon Kim, Myung-Gull Lee, Chang-Koo Shim |
| Journal | Archives of pharmacal research (Arch Pharm Res) Vol. 25 Issue 6 Pg. 969-72 (Dec 2002) ISSN: 0253-6269 [Print] Korea (South) |
| PMID | 12510855 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
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