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Uptake and biodisposition of 2-ylcyanamide-1,3,4-thiadiazole (LY217896) by red blood cells

✍ Scribed by Peter L Bonate; Albert Peyton

Publisher
John Wiley and Sons
Year
1995
Tongue
English
Weight
862 KB
Volume
16
Category
Article
ISSN
0142-2782

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✦ Synopsis

In man, I4C-2-ylcyanamide-l 3 4-thiadiazole (LY217896) accumulates into red blood cells (RBCs) where it is rapidly metabolized. Both in man and ex vivo, within a few hours of administration of 14C-LY21 7896 at least two intracellular metabolites were detected within the RBCs using HPLC. These metabolites were never detected extracellularly. After 24 h no detectable radioactivity was found in the plasma and all the radioactivity was detected within the cellular fraction. All radioactivity was identified as a single peak within the RBCs, indicating the metabolite(s) to be highly polar compared to LY217896. Parent LY217896 was never detected within the RBCs at any time point, suggesting transport, either by diffusion or a carrier mediated mechanism, was the rate limiting step. Due to the nature of the preparation it was impossible to separately characterize uptake and biotransformation. Nevertheless, uptake/biotransformation was found to be temperature sensitive, sodium independent, and energy dependent. Both niacin and vitamin B6, but not nicotinamide, competitively blocked the uptake and subsequent intracellular metabolism of LY2 17896.

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