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Model-Based Interspecies Scaling of Glucose Homeostasis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.ORCID iD: 0000-0003-1258-8297
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.ORCID iD: 0000-0003-3531-9452
2017 (English)In: CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY, ISSN 2163-8306, Vol. 6, no 11, p. 778-786Article in journal (Refereed) Published
Abstract [en]

Being able to scale preclinical pharmacodynamic response to clinical would be beneficial in drug development. In this work, the integrated glucose insulin (IGI) model, developed on clinical intravenous glucose tolerance test (IVGTT) data, describing dynamic glucose and insulin concentrations during glucose tolerance tests, was scaled to describe data from similar tests performed in healthy rats, mice, dogs, pigs, and humans. Several approaches to scaling the dynamic glucose and insulin were investigated. The theoretical allometric exponents of 0.75 and 1, for clearances and volumes, respectively, could describe the data well with some species-specific adaptations: dogs and pigs showed slower first phase insulin secretion than expected from the scaling, pigs also showed more rapid insulin dependent glucose elimination, and rodents showed differences in glucose effectiveness. The resulting scaled IGI model was shown to accurately predict external preclinical IVGTT data and may be useful in facilitating translations of preclinical research into the clinic.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017. Vol. 6, no 11, p. 778-786
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-339699DOI: 10.1002/psp4.12247ISI: 000418823400009PubMedID: 28960826OAI: oai:DiVA.org:uu-339699DiVA: diva2:1178163
Available from: 2018-01-29 Created: 2018-01-29 Last updated: 2018-01-29Bibliographically approved

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Alskär, OskarKarlsson, Mats O.Kjellsson, Maria C.
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