Walz D T, DiMartino M J, Chakrin L W, Sutton B M, MISHER A
J Pharmacol Exp Ther. 1976 Apr;197(1):142-52.
SK&F D-39162, a potential chrysotherapeutic agent, on oral administration was effective in suppressing the development of inflammatory lesions and 7S anti-sheep red blood cell antibody formation in adjuvant arthritic rats. Oral absorption of SK&F D-39162 was indicated by the presence of serum gold levels. In contrast to orally administered SK&F D-39162, gold sodium thiomalate administered intramuscularly at equivalent gold doses, appeared to be less effective in suppressing the primary and secondary lesions of adjuvant arthritis, produced relatively higher levels of gold in both serum and kidneys and produced marked toxicity. Other pharmacologic properties of SK&F D-39162 distinguishing it from gold sodium thiomalate which may have clinical significance include potent inhibitory activity on antibody-forming cells, immediate hypersensitivity reactions and extracellular release of lysosomal enzymes. In further contrast to gold sodium thiomalate, SK&F D-39162 is not a potent inhibitor of sulfhydryl group reactivity. In pharmacokinetic studies, the daily oral administration of SK&F D-39162 to normal rats produced greater stability of blood gold levels and less kidney gold accumulation than parenterally administered gold sodium thiomalate.
SK&F D - 39162是一种潜在的金制剂治疗药物,口服给药可有效抑制佐剂性关节炎大鼠炎症病变的发展及7S抗绵羊红细胞抗体的形成。血清金水平的存在表明SK&F D - 39162可经口服吸收。与口服SK&F D - 39162相比,肌肉注射等量金剂量的硫代苹果酸金钠在抑制佐剂性关节炎的原发性和继发性病变方面似乎效果较差,在血清和肾脏中产生的金水平相对较高,并产生明显的毒性。SK&F D - 39162与硫代苹果酸金钠相比具有的其他可能具有临床意义的药理学特性包括对抗体形成细胞的强大抑制活性、速发型超敏反应以及溶酶体酶的细胞外释放。与硫代苹果酸金钠进一步不同的是,SK&F D - 39162不是巯基反应性的强效抑制剂。在药代动力学研究中,与胃肠外给药的硫代苹果酸金钠相比,正常大鼠每日口服SK&F D - 39162可使血金水平更稳定,肾脏金蓄积更少。