{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T06:13:59Z","timestamp":1778134439122,"version":"3.51.4"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T00:00:00Z","timestamp":1702252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:p>Anthrax Immune Globulin Intravenous (AIGIV [ANTHRASIL]), was developed for the treatment of toxemia associated with inhalational anthrax. It is a plasma product collected from individuals vaccinated with anthrax vaccine and contains antitoxin IgG antibodies against <jats:italic>Bacillus anthracis<\/jats:italic> protective antigen. A pharmacokinetic (PK) and exposure\u2013response model was constructed to assess the PKs of AIGIV in anthrax\u2010free and anthrax\u2010exposed rabbits, non\u2010human primates and anthrax\u2010free humans, as well as the relationship between AIGIV exposure and survival from anthrax, based on available preclinical\/clinical studies. The potential effect of anthrax on the PKs of AIGIV was evaluated and estimates of survival odds following administration of AIGIV protective doses with and without antibiotic co\u2010treatment were established. As the developed PK model can simulate exposure of AIGIV in any species for any dosing scenario, the relationship between the predicted area under the concentration curve of AIGIV in humans and the probability of survival observed in preclinical studies was explored. Based on the simulation results, the intravenous administration of 420\u2009U (units of potency as measured by validated Toxin Neutralization Assay) of AIGIV is expected to result in a &gt;\u200980% probability of survival in more than 90% of the human population. Additional simulations suggest that exposure levels were similar in healthy and obese humans, and exposure in pediatrics is expected to be up to approximately seven\u2010fold higher than in healthy adults, allowing for doses in pediatric populations that ranged from one to seven vials. Overall, the optimal human dose was justified based on the PK\/pharmacodynamic (PD) properties of AIGIV in animals and model\u2010based translation of PK\/PD to predict human exposure and efficacy.<\/jats:p>","DOI":"10.1002\/cpt.3097","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T20:06:15Z","timestamp":1702411575000},"page":"248-255","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Animal\u2010to\u2010Human Dose Translation of ANTHRASIL for Treatment of Inhalational Anthrax in Healthy Adults, Obese Adults, and Pediatric Subjects"],"prefix":"10.1002","volume":"115","author":[{"given":"Martin","family":"Beliveau","sequence":"first","affiliation":[{"name":"Integrated Drug Development, Certara  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Rubets","sequence":"additional","affiliation":[{"name":"Integrated Drug Development, Certara  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Drobic","family":"Bojan","sequence":"additional","affiliation":[{"name":"Emergent BioSolutions Inc.  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