Drug metabolism and disposition: the biological fate of chemicals · 1975
Sequestration of neostigmine and metabolites by perfused rat liver.
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Somani S M, Anderson J H
Аннотация
Isolated rat livers were perfused with 0.9 to 18 mumol of 14C-neostigmine (NEO) or 14C-(3-hydroxyphenyl)trimethylammonium (HPTMA). Within 30 min. 30-90% of the administered doses were sequestered by the liver. The initial extraction rate was equivalent to about 15% of the perfusion rate. There was no evidence for saturation of the rate or the extent of sequestration of NEO or HPTMA over the dosage range examined. The amount of radioactivity in the liver remained relatively constant for several hours while NEO was converted to HPTMA and its glucuronide (G-HPTMA), plus small amounts of other metabolites. HPTMA rapidly appeared in the perfusate, but there was about an hour lag in the appearance of G-HPTMA. The concentrations of NEO and major metabolites were generally higher in the liver than in the perfusate.