ANTIARTHRITIC PROPERTIES AND UNIQUE PHARMACOLOGIC PROFILE OF A POTENTIAL CHRYSOTHERAPEUTIC AGENT - SK AND F D-39162

Abstract

SK&F D-39162 [S-triethylphosphine gold 2,3,4,6-tetra-O-1 acetyl-1-thio-.beta.-D-1 glucopyranoside] a potential chrysotherapeutic agent, on oral administration suppressed 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 Au levels. In contrast to orally administered SK&F D-39162, gold sodium thiomalate administered i.m. at equivalent Au doses, appeared less effective in suppressing the primary and secondary lesions of adjuvant arthritis, produced relatively higher levels of Au 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 Au levels and less kidney Au accumulation than parenterally administered gold sodium thiomalate.