{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:04:12Z","timestamp":1791227052360,"version":"4.1.0"},"reference-count":103,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Allometric scaling provides a practical framework for predicting human pharmacokinetic (PK) parameters from animal data by relating physiological processes to body size through power-law equations. Despite its simplicity and widespread use in first-in-human (FIH) dose selection, its predictive performance is limited by species-specific differences in absorption, distribution, metabolism, and excretion (ADME). This review summarizes the mathematical foundations, workflows, and diagnostics of allometric scaling, while critically examining where the approach succeeds and where it fails. Core concepts, including clearance, volume of distribution, correction factors, and the rule of exponents, are discussed alongside complementary methods: in vitro\u2013in vivo extrapolation (IVIVE), physiologically based pharmacokinetic (PBPK) modelling, and the Wajima normalized time-course method. Historical clinical failures, including fialuridine, TGN1412, BIA 10-2474, and rofecoxib, illustrate the limits of relying solely on allometry, while thalidomide and the fenfluramine combination exemplify toxicodynamic species-selection failures. Modern advances, including the Extended Clearance Classification System (ECCS), target-mediated drug disposition, FcRn recycling, and emerging artificial intelligence and machine-learning methods, are integrated within a framework. Overall, the review treats allometric scaling as a disciplined starting hypothesis that must be triangulated with mechanistic, experimental, and regulatory evidence to support safer and more reliable human translation.<\/jats:p>","DOI":"10.3390\/pharmaceutics18070824","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T11:39:11Z","timestamp":1783078751000},"page":"824","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Beyond Body Weight: A Comprehensive Review of Allometric Scaling in Drug Development for Human Dose Predictions"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0827-7891","authenticated-orcid":false,"suffix":"III","given":"Marlon C.","family":"Mallillin","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2H7, Canada"},{"name":"Department of Pharmacy, Faculty of Pharmacy, University of Santo Tomas, Manila 1015, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela A.","family":"Silva","sequence":"additional","affiliation":[{"name":"Simulations Plus, Inc., Lancaster, CA 93534, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3077-5790","authenticated-orcid":false,"given":"Neil A.","family":"Miller","sequence":"additional","affiliation":[{"name":"Simulations Plus, Inc., Lancaster, CA 93534, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8939-1807","authenticated-orcid":false,"given":"Shengnan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2H7, Canada"},{"name":"China Z. Pharmaceutical Productivity Centre, Beijing 101111, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7295-3896","authenticated-orcid":false,"given":"Maryam","family":"Salami","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2H7, Canada"},{"name":"Department of Food Science, Engineering and Technology, College of Agriculture and Natural Resources, Karaj Campus, University of Tehran, Karaj 31587-77871, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0919-0213","authenticated-orcid":false,"given":"Raimar","family":"L\u00f6benberg","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7050-1471","authenticated-orcid":false,"given":"Neal M.","family":"Davies","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.3733\/hilg.v06n11p315","article-title":"Body Size and Metabolism","volume":"6","author":"Kleiber","year":"1932","journal-title":"Hilgardia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1152\/physrev.1947.27.4.511","article-title":"Body Size and Metabolic Rate","volume":"27","author":"Kleiber","year":"1947","journal-title":"Physiol. 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