Browsing by Subject "protein binding"

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    From sequence to structure, to function, and back again: Integrating knowledge-based approaches with physical intuitions for protein folding, binding, and design
    (Office of the Vice Chancellor for Research, 2010-04-09) Zhou, Yaoqi
    By combining physical and knowledge-based approaches, state-of-the-art bioinformatics tools are developed for protein structure prediction, function prediction (DNA binding) and structurebased protein and ligand design.
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    Pharmacokinetic Variability of Mycophenolic Acid in Pediatric and Adult Patients with Hematopoietic Stem Cell Transplantation
    (Wiley, 2016-11) Zhang, Daping; Renbarger, Jamie L.; Chow, Diana S-L.; Department of Pediatrics, IU School of Medicine
    The aim of this study was to evaluate the pharmacokinetic variations of mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), in both pediatric and adult patients following hematopoietic stem cell transplantation (HSCT). Twenty pediatric patients with a median age of 3 years (range 0.2-12 years) and 13 adult patients with a median age of 54 years (range 18-63 years) were enrolled. Blood samples were collected on days 0, 7, 14, 21, and 30 after allogeneic HSCT. Total and free (unbound) MPA as well as MPA 7-O-glucuronide (MPAG) were quantified using a validated LC-MS/MS assay. The plasma protein binding of MPA and MPAG did not change significantly in pediatric patients over the 1-month sampling period post-HSCT. However, it increased in adult patients from day 7 to day 30 post-HSCT, from 97.3 ± 0.8% to 98.3 ± 0.6% for MPA (P < .05), and 74.6 ± 9.4% to 82.9 ± 8.1% for MPAG (P < .05). The plasma protein binding of MPA was significantly higher in males compared to females in both pediatric (98.3 ± 1.1% vs 97.4 ± 1.1%) and adult (98.1 ± 0.7% vs 97.4 ± 1.2%) patients (P < .05). The MPAG/MPA ratios on a milligram-per-kilogram dose basis in adult patients were significantly higher than those in pediatric patients (4.3 ± 3.4 vs 2.4 ± 2.6; P < .05). Time-dependent plasma protein binding and age-related differences in MPA metabolism at least in part impact the reported large intra- and interindividual variability in MPA pharmacokinetics. These patient and pharmacologic factors, if incorporated into MMF regimen design and modification, may contribute to the rational dose selection of MMF in HSCT patients.