The pharmacology unit works closely together with the team of the intervention unit. In order to support the work of the intervention unit and to support the research of other individual research groups, the Pharmacology unit provides the following services:
Many intervention studies use experimental agents that are not (yet) registered for clinical use. These investigational compounds can be obtained from the respective pharmaceutical companies, when they are willing to provide the material (usually under a strict Materials & Transfer Agreement). However, in many cases, there is a need to test combinations of agents of different sources without restrictions. We, therefore often purchase such agents from stocks of companies such as Medkoo, Selleck Chemicals or MedChem Express. Alternatively, we can have compounds through custom synthesis. Currently, we hold approximately 100 different drugs in quantities between 20 mg to 100 g quantities. We provide services in obtaining the particular compounds from the various vendors for a competitive price. We develop and/or provide advise what may be the most suitable formulation of such agents that can be used in animal studies. We perform studies to demonstrate the stability of drug formulations. We formulate and deliver drugs for preclinical studies performed by the intervention unit.
Preclinical pharmacology-pharmacokinetics studies
To be (potentially) efficacious, an agent should at least reach its target in pharmacologically meaningful quantities. In order to address this issue, we conduct pharmacokinetic studies using plasma and tissues. The sensitivity and selectivity of our LC-MS/MS systems usually allows the use of small samples volumes (5-10 μl) and minimal sample pretreatment, while still providing accurate data. This enables us to setup and validate assays for novel compounds in a relative short time frame. Moreover, it allows us to perform analyses on tail vein blood samples that can be drawn serially and thereby obtain full pharmacokinetic plasma concentration – time curves from one animal adhering to the standards of the three R’s in animal research. Many studies involve agents that specifically target specific nodes in cell signaling pathways. Usually these targets are known and assays to interrogate the (in)activation are developed by the respective research groups. Where applicable and possible, the materials that will be taken for pharmacokinetic analyses will be shared to allow both the sample preparation for drug analysis as well as for assessing target inhibition.