TY - JOUR T1 - Pharmacokinetics of Orally Administered Desferrithiocin Analogs in <em>Cebus apella</em> Primates JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1496 LP - 1498 VL - 27 IS - 12 AU - Raymond J. Bergeron AU - William R. Weimar AU - Jan Wiegand Y1 - 1999/12/01 UR - http://dmd.aspetjournals.org/content/27/12/1496.abstract N2 - The pharmacokinetic behavior of three iron chelators based on the desferrithiocin (DFT) pharmacophore, (S)-4,5-dihydro-2-(2-hydroxyphenyl)-4-thiazolecarboxylic acid (desmethyldesferrithiocin, DMDFT, 2); (S)-4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-thiazolecarboxylic acid [4-(S)-hydroxydesazaDMDFT, 3); and (R)-2-(2-hydroxyphenyl)-4-oxazolinecarboxylic acid, the oxazoline analog of desazaDMDFT, 4, is described. Although 2 and 3 are comparably effective in inducing iron excretion upon oral administration, they exhibit markedly different plasma pharmacokinetics. Ligand 2 achieves a substantially higher plasma concentration than does 3, yet the renal clearance of these compounds is similar. The oxazoline analog 4 shows poor iron clearance when administered orally, although it remains in the plasma for extended periods. Chelator 4 demonstrates a marked capacity to bind to human serum albumin compared with the thiazoline derivatives. The possible implications for designing ligands for the treatment of transfusional iron overload are discussed. The American Society for Pharmacology and Experimental Therapeutics ER -