In the development of Antibody-Directed Enzyme Prodrug Therapy (ADEPT), precise pharmacokinetics (PK) and pharmacodynamics (PD) assessments are essential. Creative Biolabs provides high-quality PK/PD services to our clients, enabling you to gain a deeper insight into the in vivo behavior and biological effects of your drugs.

Introduction

In the realm of ADEPT research, comprehensive preclinical PK/PD analyses play a crucial role in advancing the development and innovation of ADEPT drugs. These analyses not only ensure the safety and efficacy of the treatments but also contribute to the overall progress in oncology. To support this, Creative Biolabs offers a wide array of PK/PD CRO analysis services. We assist our clients in understanding the distribution, metabolism, and excretion of drugs within the body, alongside their interactions with targets and physiological effects. Moreover, through systematic PK/PD studies, our team is equipped to accurately evaluate the optimal dosing regimens, optimizing both dosage and administration frequency to enhance therapeutic efficacy while minimizing adverse effects.

Fig.1 PK/PD Model.¹

Services

Creative Biolabs has developed various ADEPT antibody coupling technology systems that enable the precise delivery of prodrugs to specific targets through their linkage with antibodies.

ADEPT leverages monoclonal antibodies to specifically target tumor cells. By attaching an enzyme to these antibodies, inactive drugs can be converted into their active forms, enhancing the effectiveness of cancer treatment while minimizing side effects. However, due to the complexity of the ADEPT approach, preclinical PK/PD analyses are essential during the drug development process. Currently, Creative Biolabs offers a full range of preclinical PK/PD analysis services, including but not limited to:

• PK Analysis Services

ADME Studies: Utilizing small animal models, Creative Biolabs conducts comprehensive assessments of the pharmacokinetic properties of ADEPT drugs, which include evaluations of bioavailability, half-life, and tissue distribution.

Plasma Concentration Monitoring: Our scientists collect blood samples at regular intervals and employ high-performance liquid chromatography (HPLC) or mass spectrometry to measure the changes in drug concentration within the body, providing vital data for subsequent dosage adjustments.

Drug Interaction Studies: We evaluate the interactions between ADEPT candidate drugs and other medications or compounds to ensure their safety.

• PD Analysis Services

Biomarker Selection and Validation: By identifying biomarkers related to targeted therapy, Creative Biolabs assists in designing well-structured preclinical experiments.

Efficacy Assessment: Through cellular assays and animal models, our laboratory evaluates the antitumor effectiveness of ADEPT therapies, confirming their targeting and selectivity.

Dose-Response Relationship Studies: Our team aids clients in determining effective dosage ranges and analyzing the relationship between drug exposure and therapeutic outcomes.

Fig.2 PK and PD Profiles.²

Case Study

In a recent project, Creative Biolabs has developed a novel ADEPT therapy aimed at the treatment of advanced melanoma. To ensure the drug's efficacy and safety, we have conducted a variety of preclinical PK/PD analyses.

1. Development of Pharmacokinetic Models:
   Our team at Creative Biolabs initially created a PK model of the drug, utilizing animal studies involving mice and guinea pigs to assess its absorption, distribution, metabolism, and excretion (ADME) characteristics. By testing various dosing regimens and administration routes, such as intravenous and subcutaneous injections, we evaluated the drug's concentration-time profiles and established a nonlinear mixed-effects model.
2. Determination of Half-Life:
   In the mouse studies, we collected serum samples to analyze drug concentrations, allowing our staff to calculate a half-life of 12 hours. This finding indicates that the drug can maintain effective concentration levels within the body for a significant duration.
3. Tissue Distribution Analysis:
   Our research team further conducted tissue distribution studies using radiolabeled drugs. The results demonstrated that the drug's concentration in tumor tissues was significantly higher than that in normal tissues, confirming the antibody's targeted characteristics.
4. Monitoring Pharmacodynamic Parameters:
   At Creative Biolabs, we measured the tumor size to evaluate the drug's efficacy in fighting tumors. Concurrently, we monitored the lifespans of mice from various dosage groups to analyze the potential survival benefits of the drug. Furthermore, we assessed the expression of specific targets within the tumor tissues and evaluated biomarkers associated with apoptosis and cell proliferation, such as Ki-67 and Caspase-3.

• Customized Experimental Design: Tailored experimental protocols to meet your specific needs, ensuring the reliability and reproducibility of your data.
• High-Throughput Analysis: Using advanced equipment to swiftly and efficiently gather PK/PD-related data, helping you reduce the research and development timeline.
• Detailed Data Interpretation and Consulting: Providing expert analysis and insights to help you gain a deeper understanding of drug behavior, supporting informed decision-making, and optimizing your strategies.
• Accurate Determination of PK Parameters: Based on high-sensitivity analytical techniques, we provide precise drug concentration-time profiles and related metrics, enhancing your understanding of the drug's behavior within the body.
• In-Depth PDAnalysis: By integrating animal model studies with clinical data, we thoroughly examine the effectiveness of targeted therapies, offering a scientific foundation for the optimization and efficacy assessment of your products.

Creative Biolabs offers professional PK/PD services for antibody drug targeting projects, ensuring that you stay at the forefront of the industry throughout every phase of drug development. Our PK/PD services encompass mature ADME analysis and multi-dimensional assessments such as target binding and effect monitoring. If you have any needs related to the development of antibody-drug targeting therapies, or if you would like to learn more about our services, please feel free to contact us!

References

1. Navarro-Guerrero, Gerardo, and Yu Tang. "Fractional-order closed-loop model reference adaptive control for anesthesia." Algorithms 11.7 (2018): 106. Distributed under Open Access license CC BY, without modification.
2. Cheng, Shen, et al. "Pharmacokinetic-pharmacodynamic modeling of tumor-targeted drug delivery using nano-engineered mesenchymal stem cells." Pharmaceutics 13.1 (2021): 92. Distributed under Open Access license CC BY 4.0, without modification.

For Research Use Only | Not For Clinical Use