Development of Physiologically Based Pharmacokinetic Model (PBPK) of BMP2 in Mice

Author(s)Utturkar, A.
Author(s)Paul, B.
Author(s)Akkiraju, H.
Author(s)Bonor, J.
Author(s)Dhurjati, Prasad
Author(s)Nohe, Anja
Ordered AuthorUtturkar A, Paul B, Akkiraju H, Bonor J, Dhurjati P, Nohe A
UD AuthorUtturkar, A.
UD AuthorPaul, B.
UD AuthorAkkiraju, H.
UD AuthorBonor, J.
UD AuthorDhurjati, Prasad
UD AuthorNohe, Anja
Date Accessioned2015-05-12T20:22:53Z
Date Available2015-05-12T20:22:53Z
Copyright DateCopyright © 2013 Utturkar A, et al.
Publication Date2013
DescriptionFinal published versionen_US
AbstractBone Morphogenetic protein 2 holds great promise for potential applications in the clinic. It is a potent growth factor for the use in the cervical spine surgery (FDA approved 2002) and has been marketed as “Infuse” for treating open tibial shaft fractures (FDA approved 2004). However, its use is limited by several significant side effects that maybe due to its potency and effect on different stem cell populations in the spine. BMP2 is expressed throughout the human body in several tissues and at a very high concentration in the blood. BMP receptors, especially BMP receptor type Ia, is ubiquitously expressed in most tissues. Currently, it is difficult to determine how BMP2 is physiologically distributed in mice or humans and no quantitative models are available. A Physiologically-Based Pharmaco-Kinetic (PBPK) model has been developed to determine steady-state distribution of BMP2 in mice. The multi-compartmental PBPK model represents relevant organ/tissues with physiological accuracy. The organs/tissue compartments chosen were brain, lung, heart, liver, pancreas, kidney, uterus, bone and fat. A blood compartment maintained connectivity among the various organs. Four processes characterized the change in the concentration of the protein in every compartment: blood flow in, blood flow out, protein turnover and receptor binding in the organ. The unique aspects of the model are the determination of elimination using receptor kinetics and generation using protein turnover. The model also predicts steady state concentrations of BMP2 in tissues in mice and may be used for possible scale-up of dosage regimens in humans.en_US
DepartmentUniversity of Delaware. Department of Chemical & Biomolecular Engineering.
DepartmentUniversity of Delaware. Department of Biological Sciences.
CitationUtturkar A, Paul B, Akkiraju H, Bonor J, Dhurjati P, et al. (2013) Development of Physiologically Based Pharmacokinetic Model (PBPK) of BMP2 in Mice. Biol Syst 2:123. doi: 10.4172/2329-6577.1000123en_US
dc.languageEnglish (United States)
PublisherOMICS Groupen_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
dc.sourceBiological Systems: Open Access
TitleDevelopment of Physiologically Based Pharmacokinetic Model (PBPK) of BMP2 in Miceen_US
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