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The University of Liverpool

The University of Liverpool (ULIV)– The United Kingdom
logo university liverpoolThe University of Liverpool is a member of the Russell group Universities in the UK.  The Department of Molecular and Clinical Pharmacology is comprised of the Centre for Drug Safety Science (CDSS), Wolfson Centre for Personalised Medicine, and a coalition of researchers with an interest in anti-infective pharmacology.  The Institute of Translational Medicine has a strong focus on research into anti-infective agents, clinical mycology, pharmacology, drug discovery and development of novel diagnostics/ biomarkers for infection.  ULIV has developed novel models if infection and used these to further define and optimise anti-infective therapy.  There is a strong interest in drug resistance, combination chemotherapy and mathematical modelling.

Main tasks
ULIV will contribute to population PK analysis in WP3 and help in the design and analysis of the clinical trial.  ULIV will also conduct the in vivo PK-PD experiments and perform the mathematical modelling/ analyses for the MRSA combination studies in WP4.  Furthermore, ULIV will contribute to modeling in other WP where specific expertise are indicated or required.

Previous experience
ULIV has state-of-the-art laboratory animal facilities along with the necessary infrastructure to conduct preclinical and clinical PK-PD studies.  There is an existing expertise and demonstrated track record in using mice, rats and rabbits along with a number of in vitro PK-PD models.  A number of different biomarkers are used to measure antimicrobial effect.  There is extensive experience in population PK modelling, development of large linked PK-PD mathematical models and Monte Carlo simulation.  These techniques have been applied for optimisation of dosing for humans and investigation of clinical relevance of antimicrobial drug resistance  ULIV receives funding from pharmaceutical industry, the National Institute of Health Research (NIHR, UK), National Institutes of Health (NIH, USA) and the Medical Research Council (MRC, UK).

Key personnel
William Hope (MBBS, PhD) was trained as an Infectious Diseases physician and Clinical Microbiologist. His research training focused on antimicrobial PK-PD with emphasis on antifungal agents.  His current work involves the optimisation of antimicrobial agents for both individuals and populations using in vivo-to-clinical bridging techniques. Dr Hope has an interest in population PK modelling, PK-PD mathematical modelling and Monte Carlo simulation.  He is currently secretary of Antifungal Susceptibility Testing subcommittee of EUCAST (European Committee on Antimicrobial Susceptibility Testing) and is also leading the development of guidelines for treatment of Candida infections in pediatric patients.

Publications
  • Hope, W. W., and G. L. Drusano. 2009. Antifungal pharmacokinetics and pharmacodynamics: bridging from the bench to bedside. Clin Microbiol Infect 15:602-12.
  • Hope, W. W., D. Mickiene, V. Petraitis, R. Petraitiene, A. M. Kelaher, J. E. Hughes, M. P. Cotton, J. Bacher, J. J. Keirns, D. Buell, G. Heresi, D. K. Benjamin, Jr., A. H. Groll, G. L. Drusano, and T. J. Walsh. 2008. The pharmacokinetics and pharmacodynamics of micafungin in experimental hematogenous Candida meningoencephalitis: implications for echinocandin therapy in neonates. J Infect Dis 197:163-71.
  • Howard, S. J., J. M. Lestner, A. Sharp, L. Gregson, J. Goodwin, J. Slater, J. B. Majithiya, P. A. Warn, and W. W. Hope. Pharmacokinetics and Pharmacodynamics of Posaconazole for Invasive Pulmonary Aspergillosis: Clinical Implications for Antifungal Therapy. J Infect Dis. 2011
  • Slater, J. L., S. J. Howard, A. Sharp, J. Goodwin, L. M. Gregson, A. Alastruey-Izquierdo, M. C. Arendrup, P. A. Warn, D. S. Perlin, and W. W. Hope. 2011 Disseminated candidiasis caused by Candida albicans with amino acid substitutions in Fks1 at position Ser645 cannot be successfully treated with micafungin. Antimicrob Agents Chemother. 

Recent publications
Attachments:
Download this file (Publications-Hope.pdf)Publications-Hope.pdf[W Hope-Publications 2010-2012]210 kB