Species-dependent binding of disopyramide enantiomers.
Serum protein binding of the basic enantiomers of disopyramide were studied in several animal species. (S)-(+)-Disopyramide was more highly bound than the (R)-(-)-enantiomer to serum protein in the man, gorilla, and pig. The reverse was true in cow serum, and in serum and albumin from sheep. Enantioselective differences in binding were due to differences in association constants. No enantioselective differences in binding were observed in serum protein from horse and goat, or in albumin from cow and pig. Disopyramide was highly bound to two sites on horse albumin. The association constant characterizing the binding of disopyramide to the first (major) site on horse albumin was 1.3 x 10(7) M-1. At predialysis concentrations of 10(-7) M, tris-(2-butoxyethyl)phosphate displaced disopyramide from sites on horse albumin and from sites on serum protein from the horse, man, gorilla, cow, and pig. At predialysis concentrations of 10(-5) M, warfarin and diazepam had no effect on disopyramide binding in these animal species. It is concluded that the enantioselective binding of disopyramide is species dependent, the site that is responsible for the moderate to high binding of disopyramide enantiomers is probably located on alpha 1-acid glycoprotein, and the sites that bind disopyramide in the horse are located on albumin and may be unique.
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002417:Cattle; D003975:Diazepam / Q000494:pharmacology; D004206:Disopyramide / Q000097:blood*; D006041:Goats; D006071:Gorilla gorilla; D006736:Horses; D009961:Orosomucoid / Q000097:blood; D011485:Protein Binding; D013045:Species Specificity; D013237:Stereoisomerism; D013552:Swine; D014859:Warfarin / Q000494:pharmacology
D001798:Blood Proteins; D009961:Orosomucoid; D014859:Warfarin; D004206:Disopyramide; D003975:Diazepam