PK/PD and Toxicology

Pharmacokinetic (PK) studies help to establish how the target host will interact with administered substances. These studies typically examine the absorption, distribution, metabolism, and excretion of the substance of interest and are useful in determining appropriate formulation and dosing schedules for novel compounds. BioModels has flexibility for designing and performing customized in vitro and in vivo PK studies, and time point collections can be customized based on your needs and timelines. After collection, samples can be further processed at BioModels for downstream analysis or sent directly to the client.

• Any mouse strain of interest
• Any rat strain of interest

• Body weight
• Timed sample collections (blood/tissue)
• In vivo or ex vivo imaging to detect fluorescence or luminescence (IVIS)

• Immunochemistry assays
• Custom assays

Pharmacodynamic (PD) studies are important for characterizing the effects exerted by novel therapeutic candidates on the host’s biological systems. These studies can help provide confirmation that the drug candidate is modulating target receptors and cellular pathways as intended and can provide insight into which biomarkers should be used to monitor efficacy in a clinical setting. Identification of biomarkers that will accurately indicate therapeutic efficacy is a primary factor in determining the success of a clinical trial. BioModels has the capabilities and expertise to execute PD studies that are custom designed to validate potentially predictive biomarkers and assess target engagement. Timed sample collections can be customized based on client needs and timelines, and samples can be further processed at BioModels for downstream analysis or sent directly to the client.

• Any mouse strain of interest
• Any rat strain of interest

• Body weight
• Timed sample collections (blood/tissue)
• Immunophenotyping
• Immunohistochemistry assays
• Immunophenotyping (Flow Cytometry)
• Multiplex cytokine analysis (Luminex)

• Custom assays

Characterizing acute toxicity levels of a candidate treatment compound in a pre-clinical setting is a necessary precursor to establishing a safe target range for dosing concentrations. BioModels has developed a non-GLP toxicology screen that will provide in vivo measurements of the lethal dose 50% (LD50) and the maximum tolerated dose (MTD) with a series of single or limited dosing followed by close observation/assessments over a 24-hour period. Doses are then increased or decreased to determine the LD50 and MTD based on initial toxicity results.

• Any mouse strain of interest
• Any rat strain of interest

• Modified Irwin procedure/functional observation battery scores
• Clinical scoring for general health and activity
• Percent weight change
• Survival rates
• Serum chemistry

• Histopathology and/or IHC analyses
• Immunophenotyping (Flow Cytometry)
• Multiplex cytokine analysis (Luminex)
• Custom assays

Tolerability, or chronic toxicology studies, are another important step in establishing a complete safety profile for novel therapeutics. These studies can help to assess the impact of continued host exposure to compounds of interest at various doses once acute toxicity levels have been determined. Tolerability studies can provide data that will be useful in establishing long-term dosing regimens and in supporting efficacy profiles for these extended treatment timelines. BioModels’ base, customizable framework for a tolerability study includes dosing for 14 days followed by close observation and serum chemistry panel analysis to detect signs of organ toxicity.

• Any mouse strain of interest
• Any rat strain of interest

• Percent weight change
• Survival
• Serum chemistry

• Histopathology and/or IHC analyses
• Immunophenotyping (Flow Cytometry)
• Multiplex cytokine analysis (Luminex)
• Custom assays