Preclinical Pharmacokinetics and Animal Toxicology
Lead Optimization
Working closely with another College core, the Vahlteich Medicinal Chemistry Core, we partner to support lead optimization projects.
Microsomal Stability
Use liver microsomes from animals and humans to compute disappearance rates and predict in vivo clearance, helping you understand the stability of your compound in vivo.
Metabolite Identification
Identify metabolites with LC-MS/MS and various scan modes and fragmentation pathways of the compound. This information guides the synthetic optimization of lead compounds by delineating the metabolic “soft-spots”.
Reaction Phenotyping
Identify the CYP enzymes involved in the metabolism of lead compounds to aid prediction of drug-drug interactions using FDA-recommended inhibitors and recombinant CYP enzymes for confirmation.
CYP Enzyme Induction
Use of real-time PCR assays for CYP expression and test enzymatic activity of induced CYP to understand your compound’s potential for clinical drug-to-drug interactions.
Protein Binding
Utilize in vitro assays such as equilibrium dialysis and ultrafiltration to help you understand the species-specific plasma protein binding.
Blood/Plasma Ratio
Access and use a well-established assay to define the blood-to-plasma ratio that is important for predicting whole-body pharmacokinetics.
Pre-Clinical Studies
Capable of performing oral bioavailability, pharmacokinetic and biodistribution studies in animal models. We have access to facilities at U-M In Vivo Animal Core to facilitate healthy disease models for a range of drug discovery and development efforts.
In Vivo Screening
Gain rapid insight into your compound’s behavior in vivo when administered by different routes.
In Vivo PK
Gain broader insights into your compound’s PK profile to support your dose translation in future disease models.
Oral Bioavailability
Understand the oral bioavailability of your compounds to aid in lead selection for further development.
Biodistribution
Ascertain tissue concentration in a specific tissue of interest and into up to 17 different target organs.
Max Tolerated Dose
Understand the acute toxicity of your compound to identify target organs affected and select doses for repeated-dose toxicity studies.
Tumor Model
Gain insight into the disposition and therapeutic effects of drugs essential to dose translation.
In vitro/In vivo ADME and Preclinical Pharmacokinetics
- Microsomal stability, Plasma stability, S9 stability, Hepatocyte stability, Cytochrome P450 inhibition, Cytochrome P450 induction and Cytochrome P450 reaction phenotyping.
- Plasma protein binding, Brain tissue binding and Blood to plasma ratio.
- Metabolite identification and soft spot identification of target compounds.
- Tissue bioanalysis, including plasma and other organs from an in vivo biodistribution study.
- Oral bioavailability of drugs in rodent models or dogs.
- Max tolerated dose with dose escalation protocol.
- In vivo screening studies with rodents to gain rapid insight into the compound’s ADME behavior.
- In vivo PK study with rodents or dogs to gain broader insight into the compound’s PK profile.
- Support customer-designed animal PK study, including tumor mouse models.
Clinical Pharmacokinetic studies
- Clinical study development.
- Data analysis with non-compartment models or non-linear mixed effects modeling.
- Modeling and simulation with Population-PK analysis.
- Precision medicine.
Questions?
If you have questions or would like to utilize our services, please reach out to us.
