Under an NIH priority to identify new drugs to treat class B parasitic agents, we performed high-throughput screens, which identified the activity of auranofin (Ridaura) against Entamoeba histolytica and Giardia intestinalis, major causes of water-and foodborne outbreaks. Auranofin, an orally administered, gold (Au)-containing compound that was approved by the FDA in 1985 for treatment of 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 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 (C max ) at day 7 was 0.312 g/ml and the half-life (t 1/2 ) 35 days, so steadystate blood levels would not be reached in short-term therapy. The highest concentration of gold, 13 M (auranofin equivalent), or more than 25ϫ the 50% inhibitory concentration (IC 50 ) for E. histolytica and 4ϫ that for Giardia, 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 g/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 broadspectrum antiparasitic drug. (This study has been registered at ClinicalTrials.gov under identifier NCT02089048.)
This is a case report of a man with decompensated cirrhosis and polysubstance abuse that was cured of chronic hepatitis C virus (HCV) infection through pharmacist active care coordination. The patient was prescribed Epclusa (sofosbuvir 400 mg/velpatasvir 100 mg) 1 tablet by mouth daily for 24 weeks, but finished his course 18 days late due to poor compliance and treatment interruptions. The active role of the clinical pharmacist in the hepatology clinic facilitated the patient’s ongoing engagement in care, leading to treatment success.
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