In vivo ADME studies, which investigate the absorption, distribution, metabolism, and excretion of substances within living organisms, utilize radiolabeling to track and quantify the fate of the compounds and their metabolites. These studies can be conducted in both rodents and non-rodents, with the choice of species dependent on those used in toxicology studies. It is crucial to maintain consistency with safety studies by employing identical dosage, route of administration, and formulations. While not mandatory for an Investigational New Drug (IND) submission, the information garnered from radiolabeled and non-radiolabeled in vivo ADME studies proves valuable in elucidating the relative clinical safety and risk to regulatory bodies such as the FDA. Alternatively, these studies may be deferred to later stages of development if their data is not immediately essential for the IND process, with their necessity arising during New Drug Application (NDA) filing.
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.
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.
Evaluating and categorizing compounds or formulations based on their pharmacokinetic profiles.
Determining the rate and extent to which a drug becomes available or is equivalent to another formulation.
Assessing how changes in dosage correspond to proportional changes in drug exposure.
Examining the linearity of drug dosage in relation to its concentration in the body, particularly with multiple doses.
Investigating the impact of interactions between different drugs on their pharmacokinetic profiles.
Studying how pharmacokinetics vary in specific populations, such as elderly individuals or those with particular health conditions.
Analyzing the distribution of a drug within various tissues, using both radioactive and non-radioactive methods.
Investigating the permeability of drugs through the blood-brain barrier, which is crucial for understanding their potential effects on the central nervous system.
Assessing the kinetics of toxic substances within the body, providing insights into their potential toxicity.
Evaluating the presence and impact of antibodies generated in response to drug administration.
Utilizing both non-compartmental and compartmental approaches to analyze drug distribution and elimination.
Developing models to understand the relationship between drug concentrations and their effects.
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.
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 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.