Pharmacokinetics and Safety Assessment Services
Rare liver diseases require precise therapeutic strategies due to their genetic heterogeneity and limited treatment options. Protheragen's integrated drug discovery platform combines high-content phenotypic screening, mechanistic validation, and translational models to accelerate candidate identification and optimization across therapeutic modalities-from small molecules to advanced cell/gene therapies. Our services streamline preclinical development, validated in disease-specific models, to advance targeted treatments for rare liver disease patients.
Overview
Rationale for Specialized PK/Safety Evaluation in Rare Liver Diseases
Pharmacokinetic (PK) and safety assessments serve as critical pillars in rare liver disease drug development, addressing unique challenges posed by genetic metabolic disorders and liver-targeted therapies. Key focus areas include characterizing altered drug metabolism pathways, evaluating tissue-specific biodistribution of liver-directed modalities, and mitigating immunogenicity risks for biologics and gene therapies in compromised hepatic environments. These studies enable data-driven optimization of therapeutic candidates while reducing clinical trial attrition.
Technological Innovations Driving Precision
Recent advancements in PK/safety assessment platforms enhance predictive accuracy and physiological relevance:
- PBPK modeling bridges preclinical-to-clinical translation, particularly for pediatric populations with rare metabolic disorders.
- Multiplexed cytokine profiling enables comprehensive immune risk assessment through simultaneous quantification of 50+ biomarkers.
- Spatially resolved LC-MS/MS imaging maps drug/metabolite distribution across liver lobules, informing target engagement strategies.
- High-parameter flow cytometry profiles immune cell dynamics post-intervention, critical for gene therapy safety monitoring.
By integrating these technologies with human-relevant in vitro models, researchers gain unprecedented resolution into ADME processes and toxicity mechanisms, accelerating the development of safer, more effective therapies for complex hepatic conditions.
Fig1. A generic physiologically based pharmacokinetic (PBPK) model. (Peng, et al., 2021)Our Services
The pharmacokinetic and safety assessment services provided by Protheragen cover the entire process from drug metabolism to toxicological evaluation, aiming to offer comprehensive support for the drug development of rare liver diseases.
Pharmacokinetics & ADME Profiling
Our pharmacokinetic services quantitatively evaluate drug absorption, distribution, metabolism, and excretion (ADME) in disease-relevant models, combining in vitro and in vivo approaches. We assess species-specific liver microsome stability, plasma protein binding via equilibrium dialysis, and biliary excretion using cannulated models to characterize metabolic behavior. Mechanistic physiologically based pharmacokinetic (PBPK) modeling supports pediatric dose scaling for metabolic disorders and first-in-human projections, integrating disease-specific pathophysiology to optimize clinical translation.
Systemic & Hepatic Safety Assessment
Comprehensive toxicity evaluations include repeat-dose studies (28-/90-day) in disease-adapted models, histopathological analysis of liver fibrosis progression via Ishak scoring, and functional biomarker monitoring (ALT/AST, bilirubin, bile acids). Advanced mitochondrial toxicity assessments using Seahorse metabolic flux analysis provide mechanistic insights into hepatotoxicity risks, ensuring robust safety profiling aligned with regulatory guidelines for rare liver diseases.
Immunogenicity Risk Characterization
We specialize in detecting humoral and cellular immune responses triggered by biologics and gene therapies. Services encompass anti-drug antibody (ADA) detection via bridging ELISA for AAV capsid immunity, neutralizing antibody assays under disease-mimicking conditions, and T-cell activation profiling using ELISpot/intracellular cytokine staining to evaluate immunotoxicity risks in compromised hepatic environments.
Mechanistic Cytotoxicity Screening
Cell-based models assess primary hepatocyte viability through ATP/MTT assays under chronic exposure, while mechanistic studies evaluate cholestasis risks via bile salt export pump (BSEP) inhibition assays. Reactive metabolite screening with CYP450 trapping identifies metabolic activation pathways, enabling early-stage de-risking of compounds with hepatotoxic potential.
Targeted Biodistribution Analysis
Quantitative mapping of therapeutic delivery includes tissue-specific vector genome quantification (qPCR/ddPCR) in liver and off-target organs, radiolabeled tracer studies, and spatial resolution of gene therapy expression patterns. These approaches validate liver-targeted delivery efficiency and monitor off-target accumulation risks.
Why Choose Us?
- Integrated Technology Platform
We offer complete drug testing services from early PK studies to safety evaluations, covering small molecules, biologics, and gene therapies. Our services include drug metabolism analysis, toxicity testing in multiple species, and detailed safety assessments.
- Customized Study Design
We create study plans based on your drug type (e.g., RNA therapies, gene therapies) and disease focus. Our designs align with regulatory requirements for clinical trials.
- Specialized Scientific Expertise
Our team has extensive experience in liver disease research and advanced testing methods. We help optimize study designs, interpret data, and address potential risks.
- Robust Data Generation
We use validated lab methods and strict quality checks to ensure reliable results for regulatory submissions.
FAQs?
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Q: What types of pharmacokinetics studies do you offer?
A: Our pharmacokinetic services include in vitro and in vivo studies to evaluate drug absorption, distribution, metabolism, and excretion (ADME).
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Q: How long does it take to complete a safety assessment project?
A: Safety assessment timelines depend on study design complexity. Standard repeat-dose toxicity evaluations (e.g., 28-day or 90-day studies in disease-relevant models) typically require 2-4 months, including histopathology review and functional biomarker analysis.
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Q: Can you help with immunogenicity testing?
A: Yes. We perform immunogenicity risk assessments for biologics and gene therapies, including anti-drug antibody (ADA) detection via bridging ELISA, neutralizing antibody assays under disease-mimicking conditions, and T-cell activation profiling using ELISpot or intracellular cytokine staining.
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Q: What technologies do you use for pharmacokinetics and safety assessment?
A: Our platform integrates LC-MS/MS for drug/metabolite quantification, high-parameter flow cytometry for immune cell profiling, spatially resolved imaging, and human-relevant in vitro models. These technologies support mechanistic insights into ADME processes, hepatotoxicity risks, and therapeutic biodistribution.
Reference
- Peng Y, Cheng Z, Xie F. Evaluation of Pharmacokinetic Drug-Drug Interactions: A Review of the Mechanisms, In Vitro and In Silico Approaches. Metabolites. 2021;11(2):75.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.