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The metabolism and disposition of LY 368842, a beta 3-adrenergic receptor agonist, were characterized in F344 rats following oral or intravenous administration of [(14)C]LY 368842. These studies were conducted as part of the investigation of the mechanism of dark liver pigmentation in LY 368842-treated F344 rats. The maximum plasma concentration of LY 368842 was reached at 3 h after an oral dose, with an elimination half-life of 4 h. The oral bioavailability of LY 368842 was determined as 8%. A tissue distribution study by quantitative whole-body autoradiography indicated high concentrations of radiocarbon in gastrointestinal contents and moderate concentrations in liver. The radiocarbon was rapidly eliminated in rats, with approximately 3% of the dose recovered in urine and 90% in faeces over 168 h. In bile duct-cannulated rats, about 42% of the dose was recovered in bile and 41% remained in the faeces. Metabolites of LY 368842 were identified in rat urine, faeces, bile and plasma samples. Oxidative metabolism of LY 368842 led to the formation of a hydroxy metabolite, an indole-2,3-dione metabolite and oxidative cleavage products such as amine and diol metabolites. Several glucuronide conjugates were also identified in rat bile. These data suggest that LY 368842 is not completely absorbed but is widely distributed, extensively metabolized and rapidly eliminated in rats after oral administration.
T L Abraham, and
T J Lindsay, and
S H Chay, and
B A Czeskis, and
M M He
October 2002,
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T L Abraham, and
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S H Chay, and
B A Czeskis, and
M M He
August 1989,
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T L Abraham, and
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S H Chay, and
B A Czeskis, and
M M He
January 1991,
Drug metabolism and disposition: the biological fate of chemicals,
T L Abraham, and
T J Lindsay, and
S H Chay, and
B A Czeskis, and
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T L Abraham, and
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M M He
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T L Abraham, and
T J Lindsay, and
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M M He
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Fundamental and applied toxicology : official journal of the Society of Toxicology,
T L Abraham, and
T J Lindsay, and
S H Chay, and
B A Czeskis, and
M M He
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Drug metabolism and disposition: the biological fate of chemicals,
T L Abraham, and
T J Lindsay, and
S H Chay, and
B A Czeskis, and
M M He
June 2006,
Drug metabolism and disposition: the biological fate of chemicals,
T L Abraham, and
T J Lindsay, and
S H Chay, and
B A Czeskis, and
M M He
February 1989,
Toxicology and applied pharmacology,
T L Abraham, and
T J Lindsay, and
S H Chay, and
B A Czeskis, and
M M He
May 1997,
Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology,
