The disposition of SK&F L-94901, a selective thyromimetic in rat, dog and cynomolgus monkey.
SK&F L-94901 is a novel thyromimetic, structurally related to thyroxine. The absorption, distribution, excretion and metabolism of radiochemically labelled [14C]-SK&F L-94901 has been investigated in the rat, dog and cynomolgus monkey. Oral absorption from solution was low or moderate in all three species. The compound was widely distributed and rapidly excreted, although traces of radioactivity were still evident in some tissues at 7 days post-dose, particularly in the kidney where radioactivity was located in an area approximating to the corticomedullary junction. Elimination of [14C]-SK&F L-94901 was both metabolic, mediated by the liver, and renal. The major metabolic routes of elimination were via oxidative deamination to lactate and acetate derivatives.
Pue
M A
MA
Department of Drug Metabolism and Pharmacokinetics, SK&F Research Ltd, Welwyn, UK.
Ransley
J A
JA
Writer
D J
DJ
Dean
A J
AJ
Franklin
E R
ER
Beattie
I G
IG
Ross
D A
DA
D000818:Animals; D001345:Autoradiography; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002415:Cats; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005243:Feces / Q000032:analysis; D008099:Liver / Q000166:cytology; D008252:Macaca fascicularis; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013970:Thyronines / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution
C050835:SK&F 94901; D013970:Thyronines