The importance of PK analysis

Following the initial in vitro screening of a new compound, it is essential to analyze how the body impacts the drug, following its administration. This is known as pharmacokinetics (PK), and it helps determining the absorption, distribution, metabolism, and elimination (ADME) of a drug. Since several factors can impact the PK of a drug, such as the body’s metabolism, it is essential to perform this assessment in a relevant animal model, which will generate predictive and translational data.

PK analysis is commonly performed by measuring the drug concentration in the blood/plasma or tissues at several timepoints after administration. PK analysis of a drug enables the calculation of key parameters, such as:

Cmax – peak concentration
Tmax – time to reach peak concentration
AUC – total drug exposure over time
t½ – half-life (time to reduce drug concentration by half)
CL – clearance rate
Vd – volume of distribution

The importance and contribution of biodistribution analysis

Analyzing the biodistribution of a drug is also very important, as it provides an insight to where the drug might accumulate. This information can provide you with a vast range of useful applications, such as assessing a patient’s response to treatment, identifying new biomarkers, or understanding the dynamics of specific cell subsets in the context of disease.

4 steps you need to follow for successful PK assessment of your compound

If you have finished the in vitro development of your lead compound and are now seeking the most suitable in vivo preclinical model to evaluate your construct’s pharmacokinetics and/or biodistribution, genOway is here to support your next steps. Choosing the appropriate model is crucial for a smooth transition to clinical trials, ensuring your findings are relevant to humans and helping you save valuable time. Using wild-type mice or the wrong humanized mice can lead to the dismissal of an otherwise great drug candidate, or to the failure to detect limitations in the half-life of the compound or on the dosing regimen.

We have developed a wide range of translational preclinical models to meet your research needs, which can be used alone or in complementary ways to maximize and accelerate your research. They are either readily available for purchase (see our Catalog Models) or can be developed specifically for you (see our Customized Models).

Our selection of catalog models includes different types of models useful for PK assessment.

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Target-specific humanized models

A wide range of target-specific humanized strains is available and ready for purchase. These models are immunocompetent, and display a physiological expression of the human target. Some of the models present in our catalog include:

The humanized SA and FcRn model (genO-hSA/hFcRn) has been validated by many companies, such as argenx and Crescendo Biologics, and is available for the assessment of therapeutics with extended half-life via FcRn recycling and/or hSA binding. We also have available models such as the genO-panhCD3/hSA/hFcRn that enable the PK testing of T-cell engagers with an increased half-life.
The humanized TFRC model (hCD71), was validated by Lundbeck and allows you to test the PK and biodistribution of constructs aiming to cross the blood-brain barrier, or of therapies targeting CD71-overexpressing cancers, as demonstrated by Bratti et al., 2024. Additionally, we have developed a new genO-hTFRC/hSA/hFcRn mouse model for improved biodistribution and drug shuttling of hSA- or hFcRn-binding compounds.
Our humanized FcγR and FcRn model is a powerful tool for PK assessment of Fc-competent therapeutic antibodies (AACR poster 2024).
Several humanized immune checkpoint models, such as the genO-hVISTA and the genO-hCD47/hSIRPα models, among many others. With these models you can assess the PK of your human-specific immunomodulators/immunotherapies, as demonstrated by Sensei Bio with a new hVISTA-targeting antibody (Thisted et al., 2024), or for biodistribution analysis to help understand treatment response and enable patient stratification (Wagner et al., 2023).

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Cell lines

Another important consideration when performing safety tests for cancer drugs is whether the tumor might impact the drug’s pharmacokinetics or mechanism of action, and whether the activation status of the immune system could also impact the drug’s safety profile. Therefore, if you would like to analyze the safety of your drug in a cancer biology context, our humanized mouse models can be used for syngeneic studies, for which a complementary catalog of cell lines is available.

A variety of cell lines, such as colon carcinoma cells lines (MC38 and CT26, for C57BL/6 and BALB/c mice, respectively) or a lymphoma cell line (EL4), are available.
These cell lines are engineered to express human proteins such as CD19 or CD20 (in the EL4 background), or humanized immune checkpoints (in MC38 and CT26 backgrounds).
We also provide a range of reporter and Knockout cell lines, which can be used as a control for your efficacy studies and target validation.

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Immunodeficient models

In our vast portfolio, you can also find immunodeficient rodents. These models can additionally be used for safety assessment in very specific cases. These include analyzing potential on- and off-target effects of CAR-T therapies or testing the safety of gene therapy. Our immunodeficient models support PDX and CDX engraftment and can develop metastasis, as well as allow longer experimental timeframes due to their extended longevity.