Butler V P, Schmidt D H, Smith T W, Haber E, Raynor B D, Demartini P
J Clin Invest. 1977 Feb;59(2):345-59. doi: 10.1172/JCI108647.
Intact sheep antidigoxin antibodies and their Fab fragments have both been found to exert profound effects on digoxin pharmacokinetics in [3H] digoxin-treated dogs. Both classes of molecule remove digoxin from the extravascular space and sequester it in the circulation in protein-bound form, a form in which the digoxin is presumably inactive. These two classes of molecule differ, however, in that the intact antibody molecules interfere with digoxin excretion, thereby promoting the retention of the glycoside; this retained digoxin is eventually released in free, active form when the administered antibody is metabolically degraded. In contrast, urinary excretion of digoxin continues in Fab-treated dogs, with significant quantities of digoxin being excreted promptly in the urine in complex with Fab fragments. These differences in urinary excretion, together with the probable decreased immunogenicity of sheep antidigoxin Fab fragments, suggest that such fragments possess potential advantages over intact antibody molecules for use in the therapy of life-threatening digoxin intoxication in man.
已发现完整的绵羊抗地高辛抗体及其Fab片段对用[³H]地高辛处理的犬的地高辛药代动力学均有深远影响。这两类分子均能将地高辛从血管外间隙清除，并以蛋白结合形式将其隔离在循环中，地高辛在这种形式下可能无活性。然而，这两类分子的不同之处在于，完整的抗体分子会干扰地高辛的排泄，从而促进糖苷的潴留；当所给予的抗体发生代谢降解时，这种潴留的地高辛最终会以游离的活性形式释放出来。相比之下，在用Fab片段处理的犬中，地高辛会持续经尿液排泄，大量地高辛会与Fab片段形成复合物迅速经尿液排出。这些尿液排泄方面的差异，以及绵羊抗地高辛Fab片段可能降低的免疫原性，表明此类片段在用于治疗人类危及生命的地高辛中毒方面比完整抗体分子具有潜在优势。
