Dr Ann Rigby-Jones

Research interests

Current Research Interests
Population pharmacokinetics & pharmacodynamics, novel drug compounds, anaesthetic drug use in patients at the extremes of weight (paediatric critical care, bariatric surgery patients),  health hazards related to use of medical plastics and dental composites (toxicokinetics)

DOCTORAL & POST-DOCTORAL RESEARCH EXPERIENCE

2000-2004 The Pharmacokinetics (PK) and Pharmacodynamics (PD) of Propofol in the Critically Ill Child, a collaboration with Professor Wolf, University of Bristol. I developed a novel solid phase extraction procedure for propofol quantification from 0.1mL whole blood. Three studies were conducted; an initial population PK study in 21 critically ill neonates, infants and children, a follow-up population PK-PD study in 10 infants and children and finally, a population analysis of pooled data (our own PK data plus data provided by 6 international research groups). These studies greatly extended the knowledge of paediatric propofol PK and PD, particularly for the smallest patients.

2003-2006 Pharmacokinetic and Pharmacodynamic Studies of Remifentanil in Paediatric Intensive Care, a collaboration with Professor Wolf, University of Bristol. I developed a novel high performance liquid chromatography assay allowing simultaneously quantification of remifentanil, fentanyl and midazolam from 0.9mL of whole blood. ‘Sparse sampling’ combined with NONMEM population modelling allowed optimal information yield from a restricted total blood sample volume whilst maximising model predictive performance. This study has provided the first description of paediatric remifentanil pharmacokinetics following infusion and has produced a model of drug disposition that can be applied to post-cardiac surgery children aged from 1 month to 9 years of age.

2005-2006 Ketamine Pharmacokinetics in Healthy Volunteers, a collaboration with Dr Absalom, University of Cambridge. I developed a new population based pharmacokinetic model for ketamine in healthy volunteers from pooled data. Retrospective evaluation shows that the predictive accuracy of our new model improves on previous inadequate models (based on suboptimal sampling schemes and non-physiological assumptions). Our new model will shortly undergo prospective evaluation prior to clinical deployment.

Industry-funded Pharmacokinetic-Pharmacodynamic Modelling Projects

2007-2008
I worked with Labopharm, Canada, assisting with the pre-clinical development of a new formulation of propofol.

2008-2012
In collaboration with the pharmaceutical industry (Maruishi, Japan) and with Veeda Clinical Research centre (Plymouth), I provided pharmacokinetic-pharmacodynamic analysis of data from Phase 1 clinical trials of a new sedative-hypnotic drug (MR04A3) and comparator compounds.

Research degrees awarded to supervised students

I currently co-supervise one Mphil/PhD student, Mr Stephen Wileman.  Steve is looking at dental composites as a potential source of human exposure to bisphenol A and plasticiser phthalates.

Studies conducted as part of Steve's work will measure plasticiser concentrations in saliva and urine before and after sealant placement in child dental patients.  Other sources of plasticiser exposure will be estimated from data gathered via a questionnaire. Baseline plasticiser concentrations in a group of adult volunteers will also be measured and correlations sought across different biological matrices in the same volunteer.  The expression of specific genes associated with endocrine pathways will be measured and correlations with plasticiser concentration evaluated, as others have recently demonstrated.  Full ethical approval for two clinical trials has now been granted and participant recruitment is under way (as of Jan 2012) and sample collection will begin shortly.