Infection Pharmacology Group

About

The Infection Pharmacology Group (Professors DJ Back, SH Khoo, A Owen, Dr GR Davies, Dr M Siccardi) is a research-active group undertaking work in pharmacology of HIV, hepatitis and TB.

Our focus is to investigate the mechanisms influencing anti-infective distribution, activity and toxicity with the aim of improving therapies. We integrate pivotal areas of research such as drug bioanalysis, pharmacokinetic modelling, molecular and cellular pharmacology, pharmacogenetics, and nanomedicine. We have developed interactive tools to improve the management of anti-infective therapies providing useful and freely available resources to healthcare workers, patients and researchers.

Molecular and Cellular pharmacology

The distribution of drugs in the human body is resulting from an interplay of different processes in several organs. We are currently working on several projects to identify proteins involved in drug distribution and characterised their action in tissues such as intestine, kidney and the liver. A number of studies are underway to both define tissue-specific patterns of expression and drug-specific substrate recognition, in order to improve our understanding of drug distribution.

Pharmacokinetic modelling

Mathematical equations have been effectively used to describe biological processes and have found extensive application in numerous pharmacology research areas.

Drug distribution can be investigated through two main different approaches:

  1. Top-down = population pharmacokinetics is a modelling approach which quantifies the sources and correlates of variability in drug concentrations among individuals using clinical data. Factors such as patient demographical, pathophysiological, and therapeutic characteristics can be associated with variability in exposure, giving a mathematical description of the drug pharmacokinetics through statistical analysis.
  2. Bottom-up = Physiologically based pharmacokinetic (PBPK) modelling is a technique which aims to simulate pharmacokinetics in populations combining system data (e.g. demographics, physiology, anatomy and genetics) describing a population of interest and in vitro drug data (e.g. Caco-2 permeability, protein binding, intrinsic clearance, lipophilicity) through a mathematical description of absorption, distribution, metabolism and elimination(ADME).The PBPK approach can therefore be applied in investigating ‘what-if’ pharmacological and clinical scenarios such as drug-drug interaction, novel formulation, pharmacogenetics and effect of comorbidities in different patient populations.

We have applied Top-Down and Bottom-Up modelling approaches to investigate a broad variety of clinical scenarios, identifying different strategies to improve the quality of the therapy or to identify safer and more effective therapeutic options.

Pharmacogenetics

Single nucleotide polymorphsims (SNPs) are an important source of genetic variability within the population. In addition, there are substantial differences between populations with respect to frequency but also to which SNPs are present. In numerous collaborations the role of SNPs in drug transporter and drug metabolism genes is currently being assessed in both a drug-specific and population-specific manner. In addition, studies are underway to assess the impact of SNPs in immunological genes that influence viral replication within the host.

HIV and HCV Drug Interactions websites

The HCV and HIV Drug Interactions website seek to monitor drug interaction data in HIV and viral hepatitis and inform where there are no data. The team, based at the University of Liverpool is responsible for constantly monitoring and updating the website content. Both sites Liverpool HIV are owned by the University of Liverpool, and operate as not-for-profit, with the following mission:

To provide a clinically useful, reliable, comprehensive, up-to-date, evidence-based drug-drug interaction resource, freely available to healthcare workers, patients and researchers.

http://www.hep-druginteractions.org/

http://www.hiv-druginteractions.org/

Bioanalytical Facility (BAF) for Drugs and Small Molecules

A GCLP-accredited facility offering a broad range of specialised and routine analytical techniques which include LC-MS, HPLC, immunoassay and high throughput biochemistry. We offer a portfolio of analyses comprising measurement of drugs (in plasma, within cells, and biological fluids such as CSF and cevicovaginal fluid) and small molecules (vitamins, hormones, peptides, biomarkers of bone health and nutrition) as well as a comprehensive range of routine biochemistry for clinical studies. In addition, bespoke assay development and validation for novel drugs and biomarkers can be undertaken.

Bioanalytical Facility Website