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Modeling of red blood cell life-spans in hematologically normal populations
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.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Farmakometri)
2012 (English)In: Journal of Pharmacokinetics and Pharmacodynamics, ISSN 1567-567X, E-ISSN 1573-8744, Vol. 39, no 5, 453-462 p.Article in journal (Refereed) Published
Abstract [en]

Despite the impact of red blood cell (RBC) Life-spans in some disease areas such as diabetes or anemia of chronic kidney disease, there is no consensus on how to quantitatively best describe the process. Several models have been proposed to explain the elimination process of RBCs: random destruction process, homogeneous life-span model, or a series of 4-transit compartment model. The aim of this work was to explore the different models that have been proposed in literature, and modifications to those. The impact of choosing the right model on future outcomes prediction-in the above mentioned areas- was also investigated. Both data from indirect (clinical data) and direct life-span measurement (biotin-labeled data) methods were analyzed using non-linear mixed effects models. Analysis showed that: (1) predictions from non-steady state data will depend on the RBC model chosen; (2) the transit compartment model, which considers variation in life-span in the RBC population, better describes RBC survival data than the random destruction or homogenous life-span models; and (3) the additional incorporation of random destruction patterns, although improving the description of the RBC survival data, does not appear to provide a marked improvement when describing clinical data.

Place, publisher, year, edition, pages
2012. Vol. 39, no 5, 453-462 p.
Keyword [en]
Life-span modeling, Red blood cells, Hba1c, Pharmacometrics, Biotin labeled, Mechanism-based model
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-183213DOI: 10.1007/s10928-012-9261-5ISI: 000308962200003OAI: oai:DiVA.org:uu-183213DiVA: diva2:562816
Available from: 2012-10-26 Created: 2012-10-23 Last updated: 2017-12-07Bibliographically approved

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Karlsson, Mats O.

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