Lima J J
Division of Pharmacy Practice, College of Pharmacy, Ohio State University, Columbus 43210-1291.
Drug Metab Dispos. 1988 Jul-Aug;16(4):563-7.
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.
在几种动物物种中研究了丙吡胺碱性对映体的血清蛋白结合情况。在人、大猩猩和猪中，(S)-(+)-丙吡胺比(R)-(-)-对映体与血清蛋白的结合更为紧密。在牛血清以及绵羊的血清和白蛋白中情况则相反。结合的对映体选择性差异是由于缔合常数的不同。在马和山羊的血清蛋白中，以及牛和猪的白蛋白中未观察到结合的对映体选择性差异。丙吡胺与马白蛋白上的两个位点高度结合。表征丙吡胺与马白蛋白上第一个（主要）位点结合的缔合常数为1.3×10⁷ M⁻¹。在预透析浓度为10⁻⁷ M时，磷酸三（2-丁氧基乙基）酯将丙吡胺从马白蛋白上的位点以及马、人、大猩猩、牛和猪的血清蛋白上的位点置换下来。在预透析浓度为10⁻⁵ M时，华法林和地西泮对这些动物物种中丙吡胺的结合没有影响。得出的结论是，丙吡胺的对映体选择性结合具有物种依赖性，负责丙吡胺对映体中度至高结合的位点可能位于α1-酸性糖蛋白上，而在马中结合丙吡胺的位点位于白蛋白上且可能是独特的。
