triethyl-phosphine-gold and Arthritis--Rheumatoid

Six gold(I) salts, some of which are used as drugs in chrysotherapy, are shown to be inhibitors of two forms of human neutrophil collagenase. The IC50 values vary over six orders of magnitude, the lowest being 3.5 nM for Myocrisin. Thus, inhibition is greatly affected by the identity of the ligands to the gold(I) atom. The inhibition of collagenase by these gold(I) salts may be a partial basis for their antiarthritic action.

Topics: Arthritis, Rheumatoid; Auranofin; Aurothioglucose; Chloromercuribenzoates; Gold; Gold Sodium Thiomalate; Gold Sodium Thiosulfate; Humans; In Vitro Techniques; Microbial Collagenase; Neutrophils; Organogold Compounds; Organometallic Compounds; Organophosphorus Compounds; p-Chloromercuribenzoic Acid; Phosphines

Serum levels after oral administration of 30 mg/kg of sodium aurothiomalate (Myocrisin), triethylphosphine gold chloride, or triphenylphosphine gold chloride to guinea pigs indicated that all were orally absorbed. However, the serum gold level of triethylphosphine gold chloride was three to four times that of Myocrisin or triphenylphosphine gold chloride and was comparable with the serum level produced when the same dose of Myocrisin was injected intramuscularly. A comparative time-course study between intramuscular administration of Myocrisin and oral administration of triethylphosphine gold chl;ride indicated that during the first 24 hours after intramuscular injection of Myocrisin, a large fraction of the gold was not protein-bound, whereas all detectable gold in serum after oral administration of triethylphosphine gold chloride was protein-bound. Gold levels in the separated protein fractions indicate that the gamma-globulin level after oral administration of triethylphosphine gold chloride is approximately three times higher after 24 hours than with intramuscular Myocrisin.

Topics: Administration, Oral; Animals; Arthritis, Rheumatoid; Biological Availability; Circadian Rhythm; Gold; Gold Sodium Thiomalate; Guinea Pigs; Injections, Intramuscular; Male; Organogold Compounds; Organophosphorus Compounds; Phosphines; Protein Binding; Serum Albumin; Serum Globulins; Time Factors