Pharmacokinetic Studies

Clinical Pharmacology and Trials Team

Section: Cancer Research UK Cancer Therapeutics Unit

Dr Florence Raynaud manages a multidisciplinary team within the Centre working in collaboration with PIramed at the development of novel PI3K inhibitors. Her group is also assessing the pharmacokinetics of novel agents in clinical trials, such as 17AAG, 17DMAG and abiraterone. In addition, the preclinical pharmacokinetics of novel chemicals under development in the Centre is evaluated. This allows prioritisation and scheduling of compounds for in vivo anti-tumour testing. Cassette dosing has been used successfully in several drug discovery projects in order to select compounds with preferred pharmacokinetic properties (CDK inhibitors in collaboration with Cyclacel and HSP90 inhibitors in collaboration with Vernalis). The thymidylate synthase inhibitors that are taken up by the α-folate receptor have been shown in vivo to accumulate specifically in tumours expressing the receptor. A number of in vitro models have been developed and validated to accelerate the throughput of preclinical studies amongst which are microsomal incubations for metabolism studies and drug–drug interaction. In vitro models of human drug absorption such as PAMPA and CaCo-2 cells are used to evaluate potential oral bioavailability of compounds.