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Blockade of these receptors broadly suppresses type 2 inflammation associated with atopic\/allergic diseases, including atopic dermatitis and asthma. Six phase 1 studies investigated the pharmacokinetics, pharmacodynamics, safety, and tolerability of dupilumab in healthy subjects. Two randomized, double\u2010blind, placebo\u2010controlled, sequential studies assessed safety and tolerability of single escalating dupilumab doses administered intravenously or subcutaneously (one included various racial groups, and one included exclusively Japanese subjects); 3 randomized, parallel\u2010group, single\u2010dose studies compared the pharmacokinetic profiles of different dupilumab products and formulations after single subcutaneous doses; and one study assessed dupilumab administered as fast versus slow subcutaneous injections. Dupilumab concentrations in serum were measured in all studies, and total immunoglobulin E (IgE) and thymus\u2010 and activation\u2010regulated chemokine (TARC) concentrations were measured in 2 studies as pharmacodynamic markers. Across the phase 1 studies, dupilumab exhibited target\u2010mediated pharmacokinetics consisting of parallel linear and nonlinear elimination, with the target\u2010mediated phase highly dominated by nonlinearity at lower drug concentrations. Systemic exposure and tolerability of dupilumab were consistent irrespective of differences in product, formulation, or racial background. Dupilumab reduced circulating concentrations of total IgE and TARC, indicating blockade of IL\u20104R\u03b1\u2013mediated signaling. Dupilumab had a favorable safety profile across the wide range of doses administered. Together, these findings support the continued development and use of dupilumab in treatment of type 2 diseases.<\/jats:p>","DOI":"10.1002\/cpdd.798","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T13:29:28Z","timestamp":1588166968000},"page":"742-755","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Dupilumab in Healthy Adult Subjects"],"prefix":"10.1002","volume":"9","author":[{"given":"Zhaoyang","family":"Li","sequence":"first","affiliation":[{"name":"Sanofi Genzyme  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen","family":"Radin","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc.  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