1989 Volume 4 Issue 4 Pages 447-457
The absorption, distribution, metabolism and excretion of 14C-labeled indometacin farnesil (14C-IMF) was studied in dogs after oral administration at the dose of 100 mg/dog or 258 mg/dog.
The peak blood concentration of radioactivity was attained at 2 hr and 8 hr after administration. The later peak was due to indomethacin (IND) released from IMF, which was suggesting the enterohepatic circulation of IND was occurred.
Radioactivity distributed into the liver, spleen and kidney was higher than that in plasma at 2 h after the 14C-IMF dosing. More than 74% of radioactivity was present as unchanged IMF in plasma, spleen, adrenal and adipose tissue, and more than 51 % in intestinal mucosa, liver and stomach mucosa, in contrary kidney in which IND and its metabolites were mainly present. Concentration of radioactivity, IMF and IND in synovial tissue at 4 hr after administration attained 0.42, 0.24 and 0.06 nmol/g, respectively, and IMF level in the tissue was about 4 times lower than that in plasma.
Subcellular distribution studies of radioactivity in liver, stomach and intestine mucosa revealed that, IMF was mainly associated with cellular membrane fraction of these tissues while IND with the cytosolic fraction.
Approximately 89 % and 11 % of administered radioactivity were excreted in feces and urine, respectively, during 7 days after administration. Radioactivity in feces consisted mainly of unchanged IMF and that in urine was mainly desbenzoyl-IND.
