Samuel Arnold

About

Dr. Samuel Arnold joined the Department of Pharmaceutics at the University of Washington as an Assistant Professor in 2023. His research predominantly focuses on characterizing exposure-response relationships for therapeutic treatment of infectious diarrhea. While there has been a substantial reduction in diarrhea-associated mortality over the past decade, diarrheal diseases remain a major global health concern, especially as the etiological landscape shifts with the reduction of rotavirus infections and the rise of other agents such as Cryptosporidium and Shigella. Dr. Arnold’s work includes developing in vitro and in vivo models for cryptosporidiosis and shigellosis, and he has led efforts to identify pharmacokinetic/pharmacodynamic (PK/PD) relationships for anti-cryptosporidiosis drugs as part of the Bill & Melinda Gates Foundation Cryptosporidium Drug Accelerator (CryptoDA). His research involves non-traditional experimental approaches to understand exposure-response relationships given the gastrointestinal localization of these pathogens. Additionally, Dr. Arnold has provided clinical pharmacology support for a clinical trial in Malawi investigating clofazimine as a potential treatment for cryptosporidiosis, and his subsequent analysis has demonstrated an association between diarrheal status and therapeutic drug exposure. His lab is working on developing pharmacokinetic models to predict the impact of diarrhea on drug exposure prior to human dosing.

Research topics

• Biology
• Virology
• Immunology
• Pharmacology
• Cell biology
• Microbiology
• Internal medicine
• Medicine
• Pathology
• Computational biology

Selected publications

• Clofazimine for Treatment of Cryptosporidiosis in Human Immunodeficiency Virus Infected Adults: An Experimental Medicine, Randomized, Double-blind, Placebo-controlled Phase 2a Trial

  Clinical Infectious Diseases · 2020 · 58 citations

  BACKGROUND: We evaluated the efficacy, pharmacokinetics (PK), and safety of clofazimine (CFZ) in patients living with human immunodeficiency virus (HIV) with cryptosporidiosis. METHODS: We performed a randomized, double-blind, placebo-controlled study. Primary outcomes in part A were reduction in Cryptosporidium shedding, safety, and PK. Primary analysis was according to protocol (ATP). Part B of the study compared CFZ PK in matched individuals living with HIV without cryptosporidiosis. RESULTS:…

  DOI

• Bumped Kinase Inhibitors as therapy for apicomplexan parasitic diseases: lessons learned

  International Journal for Parasitology · 2020 · 49 citations

  PublisherOA PDFDOI

• In vitro activity, safety and in vivo efficacy of the novel bumped kinase inhibitor BKI-1748 in non-pregnant and pregnant mice experimentally infected with Neospora caninum tachyzoites and Toxoplasma gondii oocysts

  International Journal for Parasitology Drugs and Drug Resistance · 2021 · 34 citations

  s of 165 nM (Neospora caninum) and 43 nM (Toxoplasma gondii). Immunofluorescence and electron microscopy showed that addition of 2.5 μM BKI-1748 to infected HFF monolayers transformed parasites into multinucleated schizont-like complexes (MNCs) containing newly formed zoites, which were unable to separate and form infective tachyzoites or undergo egress. In zebrafish (Danio rerio) embryo development assays, no embryonic impairment was detected within 96 h at BKI-1748 concentrations up to 10 μM.…

  DOI

• One health therapeutics: Target-Based drug development for cryptosporidiosis and other apicomplexa diseases

  Veterinary Parasitology · 2020 · 32 citations

  PublisherOA PDFDOI

• Treatment with BKI-1748 after <i>Toxoplasma gondii</i> systemic dissemination in experimentally infected pregnant sheep improves fetal and lamb mortality and morbidity and prevents congenital infection

  Antimicrobial Agents and Chemotherapy · 2024-12-31 · 6 citations

  articleOpen access

  ABSTRACT Drug development for congenital toxoplasmosis is challenging since first-line therapy has a high rate of adverse effects and exhibits suboptimal efficacy. Bumped kinase inhibitors (BKIs), targeting protein kinases with small gatekeeper residues, have been found to be effective against Toxoplasma gondii . The efficacy of BKI-1748 administered later than 2 days post-infection (p.i.), a scenario that may better reflect its real-world use as a therapeutic candidate, has not been investigate…

  PublisherDOI

Frequent coauthors

• Wesley C. Van Voorhis

  127 shared

• Ryan Choi

  124 shared

• Matthew A. Hulverson

  122 shared

• Lynn K. Barrett

  121 shared

• Kayode K. Ojo

  120 shared

• Grant R. Whitman

  118 shared

• Dustin J. Maly

  114 shared

• Lucas B. Sullivan

  105 shared

Education

• B.S., Biochemistry

  University of Colorado

• Ph.D., Pharmaceutics

  University of Washington

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