PT  - JOURNAL ARTICLE
AU  - S. M. SOMANI
AU  - J. H. ANDERSON
TI  - SEQUESTRATION OF NEOSTIGMINE AND METABOLITES BY PERFUSED RAT LIVER
DP  - 1975 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 275--282
VI  - 3
IP  - 4
4099  - http://dmd.aspetjournals.org/content/3/4/275.short
4100  - http://dmd.aspetjournals.org/content/3/4/275.full
SO  - Drug Metab Dispos1975 Jul 01; 3
AB  - Isolated rat livers were perfused with 0.9 to 18 µmol 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. The results demonstrate rapid uptake and metabolism of cationic compounds by the isolated rat liver and prolonged retention of charged metabolites within the liver. Copyright © 1975 by The American Society for Pharmacology and Experimental Therapeutics