Ex vivo experiments on femurs to assess metastatic bone strength

45e Congrès de la Société de Biomécanique, Metz, France, 26-/10/2020 - 28/10/2020Femoral fractures are a common issue for metastatic cancer patients. This type of fracture can occur during every day activities (Benca et al. 2017). Metastatic lesions can be osteoblastic, osteolytic or mixed but, mechanically, lytic lesions are more critical for the femoral strength (Benca et al. 2017). Based on a clinical scoring (Mirel's score), fracture predictions are overestimated and poorly predicted (Mirels 1989; Van der Linden et al. 2004; Benca et al. 2017), which leads to over-surgery. This scoring system is based on four following variables: metastases' site, size and type, and patient's pain (Mirels 1989). Hence, clinical studies do not focus on bone strength, but mainly on metastases characteristics and patient's pain. Finite element models, based on Quantitative Computed Tomography (QCT) imaging, were carried out to predict failure load (e.g., Kaneko et al. 2008; Tanck et al. 2009; Yosibash et al. 2014). In the context of metastatic bone, for a local validation, only one study has been published to study the major and minor principal strains using stereo-correlation (Sas et al. 2020) on cemented femur. The aim of this study was to provide experimental dataset to assess finite element models froma strain point of view

Population Pharmacokinetic Model of Plasma and Cellular Mycophenolic Acid in Kidney Transplant Patients from the CIMTRE Study

International audienceBackground and Objective Mycophenolate mofetil is widely used in kidney transplant recipients. Mycophenolate mofetil is hydrolysed by blood esterases to mycophenolic acid (MPA), the active drug. Although MPA therapeutic drug monitoring has been recommended to optimise the treatment efficacy by the area under the plasma concentration vs time curve, little is known regarding MPA concentrations in peripheral blood mononuclear cells, where MPA inhibits inosine monophosphate dehydrogenase. This study aimed to build a pharmacokinetic model using a population approach to describe MPA total and unbound concentrations in plasma and into peripheral blood mononuclear cells in 78 adult kidney transplant recipients receiving mycophenolate mofetil therapy combined with tacrolimus and prednisone. Methods Total and unbound plasma concentrations and peripheral blood mononuclear cell concentrations were assayed. A three-compartment model, two for plasma MPA and one for peripheral blood mononuclear cell MPA, with a zero-order absorption and a first-order elimination was used to describe the data. Results Mycophenolic acid average concentrations in peripheral blood mononuclear cells were well above half-maximal effective concentration for inosine monophosphate dehydrogenase and no relationship was found with the occurrence of graft rejection. Three covariates affected unbound and intracellular MPA pharmacokinetics: creatinine clearance, which has an effect on unbound MPA clearance, human serum albumin, which influences fraction unbound MPA and theABCB1 3435 C>T(rs1045642) genetic polymorphism, which has an effect on MPA efflux transport from peripheral blood mononuclear cells. Conclusion This population pharmacokinetic model demonstrated the intracellular accumulation of MPA, the efflux of MPA out of the cells being dependent on P-glycoprotein transporters. Nevertheless, further studies are warranted to investigate the relevance of MPA concentrations in peripheral blood mononuclear cells to dosing regimen optimisation