Pharmacodynamics and pharmacokinetics core facility

Pharmacokinetics (PK) is the study of what the body does to drugs. It is the mathematical study and description of the absorption, distribution, metabolism and excretion processes used by the body when a drug is administered. In order to obtain good PK data, bioanalysis forms an integral part of the science and to facilitate this we have two liquid chromatography-mass spectrometry systems (LC-MS/MS) within the facility (Figure 1). These state-of-the-art systems enable us to detect very low levels of drugs in a variety of biological matrices such as blood, plasma, tumour and cell cultures. During 2010 we developed and validated several bioanalytical methods to support both research and clinical studies. This included a validated assay to simultaneously measure capecitabine and three of its metabolites in a single sample of human plasma. Other assays include those for gemcitabine, paclitaxel, retinoic acid and azido sugars.

Figure 1
Liquid chromatography-mass spectrometry system.

During 2010 we have evaluated the use of dried blood spots (DBS) as a sampling technique for bioanalysis. Initial results are very promising and we will be developing this further in 2011. This leading edge bioanalytical technology uses small volumes of blood for sampling (typically around 30 μL). This can have a positive impact on the refinement and reduction of in vivo studies with the potential to obtain high quality PK data from efficacy studies. Michael Williams presented a poster at the European Bioanalytical Forum in Barcelona of our findings on using this technique to stabilise the degradation of pro-drugs in whole blood.

Pharmacodynamics (PD) is the study of what the drug does to the body (i.e. its effect). By relating PD effects to PK parameters, the PK/PD relationship can be determined. To this end, a variety of PD assays (e.g. biomarker assays) were established to support several clinical trials. We are looking to expand our portfolio for 2011 including evaluating the use of DBS in this field. As we are working with clinical samples the facility will be compliant to the MHRA guidelines entitled 'GCP in the Clinical Laboratory'.

In addition to the analysis of PK samples we can also offer advice on the design of PK and efficacy studies.

Facility manager
Donna Smith is head of the Pharmacodynamics and pharmacokinetics core facility.