Compounds with optimized efficacy and ADME in vitro properties are selected for in vivo studies in preclinical species
Our DMPK team designs, performs, analyses and reports pharmacokinetics (PK) experiments in rodents (both wild type and genetically modified), to support drug discovery programs. We can also offer PK experiments in large animals (dog, mini-pig and monkey), with the assistance of an external partner.
Our PK studies are fast, reproducible and use automatic sampling preparation directly from the biofluid collection tube (no tube transfer). All operations, from design to reporting, are coordinated by Watson LIMS. Depending on the goal, we can perform quantitative analysis using high sensitive multiple reaction monitoring with triple quadrupole mass spectrometers, or quantitative/qualitative analysis using HRMS with Orbitrap Q Exactive.
We set up “dilute-and-shoot” methods that enable quick analysis of very small volumes of plasma (5 µL) to obtain pharmacokinetics parameters, together with metabolite identification. The turnaround time for a PK study can be as quick as a week, with a report including all PK parameters, analytical and in-life data that are automatically retrieved from Watson LIMS.
Formulation support is provided for both single and repeated dose experiments. In particular for therapeutic peptides, oligomerization/aggregation at the dosing solution concentration is evaluated using NMR spectroscopy.
All most commonly used routes of administration are available for testing in our PK studies. Automatic blood sampling (AccuSampler®) in freely moving laboratory rats is routinely executed. Urine and feces samples can be collected for metabolite profiling and mass balance. Bile from cannulated animals can also be collected for this purpose.
All experimental procedures are executed to the highest standards of animal welfare, are compliant with all EU regulations, and approved by our Institutional Animal Care and Use Committee (IACUC).
PK studies in mice and rats, using microsampling and microdosing, can be also performed to support specific needs.
Distribution of compounds is studied using cold or radiolabelled material. Our team has extensive expertise characterizing tissue distribution of small molecules, peptides and biologics. In particular, our team is extremely experienced in analyzing tissue distribution to brain or brain sections, liver and tumors.
We can also design and execute Dose limiting toxicity (DLT) studies prior to regulatory toxicity and determine maximum tolerated dose (MTD) for in vivo studies in oncology programs.