Under an NIH priority to identify new drugs to treat Class B parasitic agents, we performed high throughput screens, which identified Auranofin's (Ridaura™) activity against Entamoeba histolytica and Giardia intestinalis, major causes of water- and food-borne outbreaks. Auranofin, an oral, gold-containing compound FDA approved in 1985 for rheumatoid arthritis, was effective in vitro and in vivo against E. histolytica and both metronidazole-sensitive and resistant strains of Giardia. We now report the results of an NIH sponsored Phase I trial to characterize the PK and safety of auranofin in healthy volunteers using modern techniques to measure gold levels. Subjects received 6 mg po of auranofin daily, the recommended dose for rheumatoid arthritis, for 7 days and were followed for 126 days. Treatment Associate Adverse Events were reported by 47% of the subjects, but all were mild and resolved without treatment. The mean plasma gold Cmax at Day 7 was 0.312 μg/mL and t1/2 35 days, so steady state blood levels would not be reached in short term therapy. The highest concentration of gold was in feces at 7 days, 13 μM (auranofin equivalent), or more than 25X the IC50 for E. histolytica and 4X for Giardia. Modeling of higher doses (9 and 21 mg/day) was performed for systemic parasitic infections, and plasma gold levels of 0.4-1.0 mcg/mL were reached after 14 days of 21 mg/day. This Phase I trial supports the safety of auranofin and provides important PK data to support its potential use as a broad spectrum antiparasitic drug.
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