title: A physiologically based pharmacokinetic model for strontium exposure in rat.
abstract: OBJECTIVE
  To develop a physiologically based pharmacokinetic (PBPK) model to describe the disposition of Strontium--a bone seeking agent approved in 2004 (as its Ranelate salt) for treatment of osteoporosis in post-menopausal women.
  
  
  METHODS
  The model was developed using plasma and bone exposure data obtained from ovariectomised (OVX) female rats--a preclinical model for post-menopausal osteoporosis. The final PBPK model incorporated elements from literature models for bone seeking agents allowing for description of the heterogeneity of bone tissue and also for a physiological description of bone remodelling processes. The model was implemented in MATLAB in open and closed loop configurations, and fittings of the model to exposure data to estimate certain model parameters were carried out using nonlinear regression, treating data with a naïve-pooled approach.
  
  
  RESULTS
  The PBPK model successfully described plasma and bone exposure of Strontium in OVX rats with parameter estimates and model behaviour in keeping with known aspects of the distribution and incorporation of Strontium into bone.
  
  
  CONCLUSIONS
  The model describes Strontium exposure in a physiologically rationalized manner and has the potential for future uses in modelling the PK-PD of Strontium, and/or other bone seeking agents, and for scaling to model human Strontium bone exposure.
authors.affiliation: Department of Molecular and Clinical Pharmacology, The University of Liverpool, Block H, 1st Floor 70 Pembroke Place, Liverpool L60 3CE, UK. henry.pertinez@liverpool.ac.uk
authors.forename: Henry
authors.initials: H
authors.lastname: Pertinez
authors.forename: Marylore
authors.initials: M
authors.lastname: Chenel
authors.forename: Leon
authors.initials: L
authors.lastname: Aarons
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects; D005260:Female; D006801:Humans; D008954:Models, Biological; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000378:metabolism* / Q000601:surgery; D010052:Ovariectomy / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013324:Strontium / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D013324:Strontium
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