Proficient researchers at Vipragen are adept at planning and executing PK studies to evaluate various parameters, facilitating regulatory submissions through the utilization of radiolabeled or nonradiolabeled test articles. Our comprehensive analytical support encompasses radioassay, LC-MS/MS, HPLC, CE, or immunochemistry. Toxicokinetic assessments can be conducted simultaneously with ongoing toxicology programs, ensuring compliance with GLP requirements.

In Vivo PK Studies

• » Rank-ordering compounds/formulations
• » Bioavailability and bioequivalence
• » Dose proportionality (ascending dose)
• » Dose linearity (multiple dose)
• » Drug-drug interactions
• » Special populations
• » Tissue distribution (non-radioactive and radioactive)
• » Blood brain barrier
• » Toxicokinetics
• » Anti-drug antibodies
• » Non-compartmental and compartmental pharmacokinetics
• » Pharmacodynamic and pharmacokinetic/pharmacodynamics modeling
• » Input into study design, including preclinical-to-clinical considerations (allometric scaling and human equivalent dose projections)

Routes of Administration and Sample Collection

• » Diverse dosing approaches: single agents, cassette dosing, single dose, and repeat dose
• » Administration via various routes: PO, IV, IP, SC, etc.
• » Serial sampling implemented across all species
• » Utilization of microsampling techniques
• » Collection of tissues, urine, and CSF
• » Bile collections conducted through bile duct cannulation (BDC)
• » Comprehensive and integrated bioanalysis services provided

Models for Surgical Procedures:

• » Bile duct cannulation
• » Vascular access ports
• » Portal vein cannulation
• » Intestinal access ports

Vipragen's veteran researchers conduct pharmacokinetic (PK) studies, crucial for regulatory submissions. These studies, using radiolabeled or nonradiolabeled test articles, utilize diverse analytical methods like radioassay, LC-MS/MS, HPLC, CE, or immunochemistry. Toxicokinetic assessments are efficiently conducted in tandem with toxicology programs, ensuring Good Laboratory Practice (GLP) compliance. In vivo PK studies encompass a comprehensive array of assessments, aiming to understand the behavior of compounds or formulations within living organisms.

Rank-Ordering Compounds/Formulations:

Evaluating and categorizing compounds or formulations based on their pharmacokinetic profiles.

Bioavailability and Bioequivalence:

Determining the rate and extent to which a drug becomes available or is equivalent to another formulation.

Dose Proportionality (Ascending Dose):

Assessing how changes in dosage correspond to proportional changes in drug exposure.

Dose Linearity (Multiple Dose):

Examining the linearity of drug dosage in relation to its concentration in the body, particularly with multiple doses.

Drug-Drug Interactions:

Investigating the impact of interactions between different drugs on their pharmacokinetic profiles.

Special Populations:

Studying how pharmacokinetics vary in specific populations, such as elderly individuals or those with particular health conditions.

Tissue Distribution (Non-Radioactive and Radioactive):

Analyzing the distribution of a drug within various tissues, using both radioactive and non-radioactive methods.

Blood-Brain Barrier:

Investigating the permeability of drugs through the blood-brain barrier, which is crucial for understanding their potential effects on the central nervous system.

Toxicokinetics:

Assessing the kinetics of toxic substances within the body, providing insights into their potential toxicity.

Anti-Drug Antibodies:

Evaluating the presence and impact of antibodies generated in response to drug administration.

Non-Compartmental and Compartmental Pharmacokinetics:

Utilizing both non-compartmental and compartmental approaches to analyze drug distribution and elimination.

Pharmacodynamic and Pharmacokinetic/Pharmacodynamics Modeling:

Developing models to understand the relationship between drug concentrations and their effects.

Input into Study Design:

Providing essential information for the design of further studies, including considerations for transitioning from preclinical to clinical phases, involving allometric scaling and projections of human equivalent doses.

In vivo PK studies cover a broad spectrum of assessments that contribute valuable insights into the pharmacokinetic behavior of compounds, influencing study design and supporting the development and regulatory evaluation of pharmaceuticals.

Metabolism involves the study of how a drug undergoes metabolic processes within a living organism. It includes the systematic analysis and identification of metabolites formed during these processes, providing critical insights into the drug's transformation, potential bioactivity, and toxicity. The evaluation of pharmacokinetics, whether non-radiolabeled or radiolabeled, is integral to understanding the drug's behavior, absorption, distribution, metabolism, and excretion patterns within the body. This research is essential for optimizing drug development, ensuring efficacy, and addressing safety concerns in clinical applications.

Metabolite Profiling/Identification

In the realm of in vivo ADME (Absorption, Distribution, Metabolism, and Excretion) studies, a pivotal aspect is the meticulous exploration of drug metabolism through metabolite profiling and identification. This entails a systematic and comprehensive analysis to discern the various metabolites generated as a drug undergoes metabolic transformations within a living organism. The significance of this lies in unravelling the intricate metabolic pathways, shedding light on the potential formation of bioactive or toxic metabolites. Through advanced analytical techniques such as mass spectrometry and nuclear magnetic resonance, researchers can separate, detect, and identify these metabolites. This information proves crucial for understanding the safety and efficacy of a drug, as well as guiding subsequent decisions in the drug development process.

Pharmacokinetics (Non-Radiolabelled and Radiolabelled):

Pharmacokinetics assessment in in vivo ADME studies comprises non-radiolabelled and radiolabelled approaches. Non-radiolabelled methods, using LC-MS or HPLC, quantitatively evaluate drug concentrations in biological samples, offering insights into absorption, distribution, metabolism, and excretion. Radiolabelled pharmacokinetics involves tracking drugs labelled with a radioactive isotope, providing precise quantification through radio assays. This method is advantageous for studying drugs at low concentrations, ensuring heightened sensitivity in understanding pharmacokinetic parameters. Both approaches are crucial for delineating drug fate in living organisms, contributing essential data for optimizing drug development and ensuring clinical safety.

Modelling and simulation are vital for understanding in vivo Absorption, Distribution, Metabolism, and Excretion (ADME) of drugs. This involves creating mathematical models to predict dynamic processes within the body. ADME modelling quantifies drug fate, aiding in drug development optimization by providing insights into factors influencing pharmacokinetics. In vivo simulation replicates physiological processes, predicting a drug's behaviour before clinical trials and identifying optimal dosing regimens. Integrating DMPK principles enhances prediction accuracy by incorporating drug metabolism and pharmacokinetic data into models. Advantages include cost-effectiveness, time efficiency, and proactive risk mitigation by identifying potential issues early in drug development. Modelling and simulation offer invaluable tools for drug developers to gain predictive insights, optimize dosing regimens, and make informed decisions throughout the drug development process.

Vipragen offers comprehensive bioanalytical services for both novel biologics and biosimilars, covering in vitro and in vivo studies for regulatory and non-regulatory purposes. Our specialized group excels in developing, validating, and analysing quantitative LC-MS/MS methods seamlessly across all stages of compound development. Tailored methods for discovery studies and GLP-compliant bioanalysis for regulatory submissions are provided. Our proficient team develops highly sensitive LC-MS/MS methods for various analytes, metabolites, pro-drugs, and compounds, routinely establishing and validating analytical methodologies across different species. With expert technical staff, cutting-edge equipment, on-site Quality Assurance, and extensive bioanalysis experience, Vipragen delivers timely and reliable services for routine and complex studies.

Our capabilities include:

• » Successful development and validation of bioanalytical methods for various compounds.
• » Provision of bioanalytical services supporting GLP IND-enabling study packages for FDA, EMEA, MHRA, and other global regulatory submissions, as well as studies requiring analytical support.
• » Proficiency in developing and validating bioanalytical methods using state-of-the-art LC-MS/MS and HPLC instrumentation, achieving sensitivity down to picogram levels.
• » Customized method development for non-GLP bioanalysis.
• » Sample processing expertise using precipitation, liquid-liquid extractions, and solid-phase extractions.
• » Capability for derivatization approaches, particularly for poorly ionizable compounds, including method development and validation.
• » Quantification of analytes and metabolites in diverse biological matrices such as plasma, serum, and blood samples, ensuring compliance with the latest regulatory requirements of USFDA, EMEA, etc.
• » Experience in developing methods for various matrices, including urine, feces, CSF, bile, and various tissue homogenates.
• » GLP bioanalysis to support preclinical bioequivalence studies.
• » Expertise in handling specialized formulations such as liposomes.
• » Equipped with Watson LIMS – a 21 CFR Part 11 compliant Data Management System for meticulous data handling.