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The disposition of SK&F L-94901, a selective thyromimetic in rat, dog and cynomolgus monkey

Summary

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 l ow 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.

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Abbreviations

m:

multiplet

q:

quartet

t:

triplet

d:

doublet

s:

singlet

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Correspondence to M. A. Pue.

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Pue, M.A., Ransley, J.A., Writer, D.J. et al. The disposition of SK&F L-94901, a selective thyromimetic in rat, dog and cynomolgus monkey. European Journal of Drug Metabolism and Pharmacokinetics 14, 209–219 (1989). https://doi.org/10.1007/BF03190101

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Key words

  • Tissue distribution
  • metabolism
  • excretion
  • thyromimetic
  • thyroxine