Pharmacokinetic (PK) and biodistribution characterization of therapeutic proteins and peptides is a hot topic in the pharmaceutical industry, especially as the catalog of novel therapeutic proteins and peptides continues to grow. Understanding the PK profile of a given therapeutic protein/peptide is an important factor in assessing its efficacy and safety, which helps determine the appropriate dose, route of administration, and dosing schedule during preclinical and clinical studies. CD Formulation offers a full range of PK testing services for your therapeutic protein/peptide to support any protein/peptide drug modality at any stage of development.

The Importance of PK Studies for Proteins and Peptides

PK studies are essential for evaluating the absorption, distribution, metabolism, and excretion of drugs in the body. For large, complex molecules such as proteins and peptides, PK studies are an important step in their development as therapeutic entities, allowing for:

• Understand absorption and distribution: Proteins and peptides are typically administered by injection or infusion because of their large size and susceptibility to degradation in the gastrointestinal tract. PK studies help determine how these molecules are absorbed and distributed in the body, providing valuable information about their bioavailability and tissue targeting.
• Optimize dosing and administration: PK studies provide insight into the pharmacokinetic parameters of proteins and peptides, such as clearance, half-life, and volume of distribution. This information is essential for designing dosing regimens that achieve therapeutic levels in the body and keep drug concentrations within the desired range.
• Predict drug interactions: Proteins and peptides may interact with other drugs or compounds in the body, affecting their pharmacokinetics and potentially causing adverse effects or reduced efficacy. PK studies help identify potential drug interactions and guide dose adjustments to minimize their effects.
• Support regulatory approval: PK data are a key component of regulatory applications for drug approvals, providing evidence of the safety, efficacy, and pharmacokinetic characteristics of proteins and peptides. Comprehensive PK studies are essential to demonstrate the pharmacology of these molecules and ensure their successful development and commercialization.

Fig.1 Key in vitro and in vivo data to characterize the pharmacokinetic and biodistribution of therapeutic proteins during drug development. (Ball K, et al., 2022)

Explore Our Proteins & Peptides PK Studies

Before each batch of biopharmaceuticals enters clinical testing or release, its absorption, distribution, metabolism, and excretion data must be confirmed to provide key guidance data for clinical studies and ensure their safety and efficacy. At CD Formulations, our experienced protein and peptide experts will work closely with you to explore the best solution for your therapeutic protein/peptide PK testing to ensure your product successfully enters the clinical stage or is released to the market.

Thanks to decades of experience in using advanced PK analysis platforms, our PK analysis team is able to choose the best strategy for your project based on your drug characteristics and regulatory guidance. We have extensive experience in protein/peptide PK analysis method development and validation and can provide the following services to evaluate the PK behavior of your therapeutic protein/peptide drug development process at all stages.

• Protein and peptide PK test analytical method development.
• Optimization of existing protein and peptide PK test analytical methods.
• Verification of PK test analytical methods for accuracy, precision, linear range, specificity, robustness, and LOD/LOQ according to ICH drug requirements.
• Protein and peptide tissue distribution studies (single-dose tissue distribution studies and repeated-dose tissue distribution studies).
• Protein and peptide PK studies.
• Early ADME and PK screening.
• ADME and PK mechanism investigation.
• Support for regulatory submission of ADME data.
• Transfer of PK test analytical methods for proteins and peptides.
• Support for batch release testing.

Our Administration Pathways for Proteins/Peptides

• Administration by Injection or Infusion
• Inhalational Administration
• Intranasal Administration
• Transdermal Administration
• Peroral Administration

What Research Subjects Do We Work With?

• Mice/rats.
• guinea pigs.
• Rabbits.
• Canines.
• Pigs/minipigs.
• Non-human primates (NHPs).

Our Technology Platforms

In our analytical laboratories, systemic concentrations of therapeutic proteins/peptides are determined in blood, plasma, or serum collected from the relevant animal species and quantified using ligand binding assays such as ELISA, electrochemiluminescence (ECL), or mass spectrometry such as liquid chromatography-tandem mass spectrometry or liquid chromatography-high resolution mass spectrometry.

Biodistribution data are characterized by collecting tissue samples and measuring protein/peptide concentrations by a range of bioanalytical methods. Alternatively, in vivo biodistribution can be measured in intact animals by radiolabeling or fluorescence conjugation followed by measurement by positron emission tomography, immunofluorescence, or other imaging techniques.

Typical protein/peptide concentration characterization techniques include ELISA, liquid chromatography-tandem mass spectrometry (LC-Tandem MS), liquid chromatography-high resolution mass spectrometry, matrix-assisted laser desorption ionization, or radiolabeled analysis by quantitative whole-body autoradiography.

Our Expertise

Preclinical development of therapeutic proteins/peptides requires consideration of multiple factors, including efficacy, toxicology, and ADME properties, as well as various other developability aspects.

During early discovery and development, we support the use of in vitro and in vivo models to screen multiple drug candidates and generate in vitro-in vivo correlations (IVIVC) to help you design therapeutic proteins/peptides with desirable PK and biodistribution properties, such as systemic half-life or specific biodistribution in one or more tissue types.

Our expertise includes:

• Evaluation of candidate protein/peptide molecular properties: This involves evaluating these molecular properties in various early developability assays, including specific or nonspecific binding to cell membrane proteins, FcRn interaction evaluation, self- and cross-interactions, and multispecificity.
• Quantitative structure-pharmacokinetic relationship (QSPKR) studies: Enrichment of proteins and peptides with desirable PK properties using QSPKR in silico approaches.
• Binding affinity and internalization studies of target antigens: In vitro assays are performed to measure equilibrium rate constants (KD) and binding kinetics of therapeutic protein/peptide binding to target antigens.
• Studies of the effects of molecular properties on PK and biodistribution: The effects of FcRn affinity, charge, size, route of administration, etc. are evaluated by assessing the relationship between the physicochemical and in vitro properties of the proteins/peptides and their target-independent PK and biodistribution. Assessment of systemic PK as well as tissue concentrations is usually performed using radioactive or fluorescently labeled proteins/peptides.

Why Choose Us for Proteins & Peptides PK Studies?

• We have a team of experts with rich experience in developing PK analysis methods for protein/peptide biologics.
• We are familiar with the industry practices and regulatory requirements for developing and validating acceptable PK analysis methods for protein/peptide biologics.
• We provide high-quality PK studies and results that strictly comply with GLP and GCP regulations and international regulatory standards (FDA, EMEA, ICH).
• We perform dozens of protein and peptide biopharmaceutical PK Studies projects every year.
• We offer flexible experimental designs and customized solutions.

Publication

CD Formulation has extensive expertise in analytical method development and PK studies of therapeutic proteins and peptides, providing you with insights into your products and accelerating your development process. Please feel free to contact us to speak with our team of scientists and learn how our expertise and technology can support your product development.