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The binding to various proteins and the uptake by erythrocytes of 14C-KT1 -32 and its major metabolites (14C-M1, 14C-M2) were studied. The binding of 14C-KT1-32, 14C-M1 and 14C-M2 to total plasma, albumin, α1-acid glycoprotein(AAG) and γ-globulins were determined in humans and various animals in vitro, ex vivo and in vivo. The uptakes by erythrocytes were determined in humans, rats and dogs in vitro or in vivo.1. The binding of 14C-KT1-32, 14C-M1 and 14C-M2 to plasma and albumin were greater than 97%. AAG and γ-globulins bindings of 14C-KT1-32, 14C-M1 and 14C-M2 were less than 15%.2. Protein binding of 14C-KT1-32 to rat, dog and human plasma was characterized as reversible.3. Protein binding of 14C-KT1-32 to human plasma was not affected by the additions of cimetidine, ranitidine, famotidine and bromazepam. Protein binding of 3H-cimetidine, ranitidine, famotidine and bromazepam to human plasma was also not affected by the addition of KT1-32.4. The uptakes of 14C-KT1-32 by erythrocytes of humans and various animals were less than 41% in vivo or in vitro.

Studies on the metabolic fate of azuletil sodium. V: Protein binding and uptake by erythrocytes.