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Auranofin, an orally administered, gold (Au)-containing compound that was approved by the FDA in 1985 for treatment of rheumatoid arthritis, was effective<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>against<jats:named-content content-type=\"genus-species\">E. histolytica<\/jats:named-content>and both metronidazole-sensitive and -resistant strains of<jats:named-content content-type=\"genus-species\">Giardia<\/jats:named-content>. We now report the results of an NIH-sponsored phase I trial to characterize the pharmacokinetics (PK) and safety of auranofin in healthy volunteers using modern techniques to measure gold levels. Subjects received orally 6 mg (p.o.) of auranofin daily, the recommended dose for rheumatoid arthritis, for 7 days and were followed for 126 days. Treatment-associated adverse events were reported by 47% of the subjects, but all were mild and resolved without treatment. The mean gold maximum concentration in plasma (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) at day 7 was 0.312 \u03bcg\/ml and the half-life (<jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub>) 35 days, so steady-state blood levels would not be reached in short-term therapy. The highest concentration of gold, 13 \u03bcM (auranofin equivalent), or more than 25\u00d7 the 50% inhibitory concentration (IC<jats:sub>50<\/jats:sub>) for<jats:named-content content-type=\"genus-species\">E. histolytica<\/jats:named-content>and 4\u00d7 that for<jats:named-content content-type=\"genus-species\">Giardia<\/jats:named-content>, was in feces at 7 days. Modeling of higher doses (9 and 21 mg\/day) was performed for systemic parasitic infections, and plasma gold levels of 0.4 to 1.0 \u03bcg\/ml were reached after 14 days of treatment at 21 mg\/day. This phase I trial supports the idea of the safety of auranofin and provides important PK data to support its potential use as a broad-spectrum antiparasitic drug. (This study has been registered at ClinicalTrials.gov under identifier NCT02089048.)<\/jats:p>","DOI":"10.1128\/aac.01947-16","type":"journal-article","created":{"date-parts":[[2016,11,8]],"date-time":"2016-11-08T03:54:40Z","timestamp":1478577280000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":129,"title":["Phase I Clinical Trial Results of Auranofin, a Novel Antiparasitic Agent"],"prefix":"10.1128","volume":"61","author":[{"given":"Edmund V.","family":"Capparelli","sequence":"first","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Bricker-Ford","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. John","family":"Rogers","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James H.","family":"McKerrow","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon L.","family":"Reed","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Medicine, University of California, San Diego, School of Medicine, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.37.26051"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.1.150-164.2001"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/clind\/15.3.464"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/322038"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2.6.529"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2758"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01675-12"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.4161\/gmic.22596"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003534"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002973"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl541"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-011-0997-9"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.020701"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040206"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-9114.1983.tb03277.x"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1080\/15027732.1986.12461436","article-title":"Pharmacology of auranofin: overview and update","volume":"63","author":"Gottlieb NL","year":"1986","unstructured":"Gottlieb NL . 1986. 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