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The in vivo and in vitro characterization of N‐ButylPyridinium Chloride transport and elimination
Author(s) -
Cheng Yaofeng,
Kuester Robert,
Knudsen Gabriel,
Wright Stephen,
Sipes I Glenn
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1132.1
Subject(s) - chemistry , bioavailability , toxicokinetics , chloride , urine , amine gas treating , in vitro , in vivo , nuclear chemistry , pharmacology , organic chemistry , biochemistry , toxicity , medicine , microbiology and biotechnology , biology
N‐ButylPyridinium Chloride (NBuPy‐Cl) is a quaternary amine organic chemical that is known as ionic liquid with solvent properties. In male F‐344 rats, it is readily absorbed in the GI tract (oral bioavailability 65%), with 86% of the absorbed dose eliminated in the urine in 12 hours as parent compound. Toxicokinetic analysis of NBuPy‐Cl revealed its systemic clearance to be 6.4‐9.0 ml/min. This rapid clearance and its chemical structure suggest that NBuPy‐Cl might be secreted by organic cation transporters (OCTs) in the nephron. To address this, the transport of NBuPy‐Cl was characterized in vitro using Chinese Hamster Ovary cells with stably expressed human OCTII. NBuPy‐Cl was effectively transported by hOCTII (K t =11.0 μM). It was also a potent inhibitor (IC 50 =1.6 μM) of another substrate, tetraethyl ammonium, that is transported by hOCTII. These data suggest that OCTII mediated transport of NBuPy‐Cl facilitates its rapid clearance from blood and appearance as parent compound in the urine. This research was supported by the NIEHS NTP Grant No. N01‐ES‐45529 and NIEHS‐sponsored Southwest Environmental Health Science Center Grant Number P30‐ES‐06694.