At PsychoGenics, we recognize the critical nature of reliable preclinical pharmacokinetic and pharmacodynamic services. What sets us apart is our commitment to providing both consistency and quality, all under one roof. This integrated approach simplifies project management, minimizes risks, and reduces time to receive your data.
Comprehensive PK Study Options for Dosing, Sampling and Bioanalysis
PsychoGenics offers a wide range of options for your rodent in vivo discovery PK studies. In addition to standard dose administration routes such as oral (PO), intravenous (IV), subcutaneous (SC), intraperitoneal (IP), intramuscular (IM), we are skilled at surgery-assisted routes directly into the CNS space such as intracerebroventricular (ICV). We provide an extensive set of sample collection and processing choices for blood, CSF, and tissues, ensuring we cater to the specific sampling requirements of your study.
Our PK sample bioanalysis capabilities for the measurement of exogenous molecules cover your small molecule and protein therapeutic modalities using our ultra performance liquid chromatography (UPLC) with tandem mass spectroscopy (MS/MS), electrochemical detection (ECD), or ELISA based assay systems including MesoScale (MSD) and Luminex.
Combining PD Endpoints
PsychoGenics offers combined preclinical PK and PD studies, enabling a comprehensive understanding of the relationship between drug exposure and its desired therapeutic response, allowing for optimization of dose regimens and prediction of clinical efficacy. PsychoGenics’ full range of capabilities can be deployed to measure PD effects.
- Behavioral and In Vivo Testing
- EEG Studies
- Receptor Occupancy
- Histology and Immunohistochemistry
- Microdialysis
- Ex Vivo Sample Biomarker Analysis
Establishing Pharmacokinetic-Pharmacodynamic (PK/PD) Relationships
PsychoGenics has established methods and assays to measure drug levels from plasma, urine, tissues including brain, spinal cord, and various organs, cerebrospinal fluid (CSF) and extracellular fluid (ECF), the latter by equilibrium in vivo microdialysis. Bioanalysis is conducted using LC-MS/MS for small molecules and peptides (up to 6000 kDa depending on the peptide), or ELISA-based assays such as Meso Scale Discovery (MSD) for measuring larger molecules.
PsychoGenics offers pharmacokinetic (PK) capabilities to guide dosing, route of administration, and determine the levels of drug over a time course.
Plasma-concentration time course in both mice and rats were measured by LC-MS/MS following oral (PO) or intravenous (IV) administration of a test compound.
Brain and plasma exposure can be analyzed following behavioral testing to correlate drug level with behavioral efficacy.
Oral administration of a test compound significantly decreased immobility in the rat Forced Swim Test, a preclinical assay to detect antidepressant efficacy, in a dose-dependent manner. Plasma and brain exposure analysis showed a dose-dependent increase in drug levels that correlated with the behavioral efficacy data. Similar relationships can be evaluated with more than 60 behavioral assays offered at PsychoGenics.
Drug levels and their corresponding effect on neurotransmitter measures in brain ECF can both be performed using microdialysis sampling in combination with LC-MS/MS analyses, providing PK/PD relationships.
(A) ketamine increases striatal dopamine levels in rats in a dose-dependent manner. (B) Brain ECF levels of ketamine and its metabolites peak concurrently with the rise in dopamine levels.
Receptor occupancy aids in understanding the relationship between dose, plasma concentration, and brain exposures, establishing PK/PD relationship profile for test compounds. PsychoGenics can measure receptor occupancy in the rodent brain, spinal cord, or other organs using radiolabeled or non-labeled tracers for the target of interest.
Correlation between ex vivo receptor occupancy of the 5-HT1B receptor and the free concentration of a compound developed at PGI in rat plasma and brain following oral administration. Data show excellent correlation between unbound drug concentration in both plasma and brain and receptor occupancy measured by displacement of 3HGR125743, a 5HT1B selective antagonist.