Pharmacokinetics and Drug Metabolism

In the early stages of drug development, understanding how a compound is distributed and metabolized throughout the body is crucial for predicting its therapeutic potential and safety profile. Systemic delivery is fundamental in preclinical research because it ensures that the investigational drug reaches all relevant tissues and organs, mimicking how the drug would be distributed in humans. This exposure allows for a comprehensive evaluation of the drug’s pharmacokinetics (PK), including absorption, distribution, metabolism, and excretion (ADME), as well as its efficacy and potential toxicity. By simulating human-like distribution in animal models, we can gain early insights into a compound's behavior, aiding in more informed decision-making for further clinical development.

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Understanding the pharmacokinetics of a drug provides a solid foundation for optimizing its design. It allows researchers to identify key properties, such as bioavailability and half-life, which influence how effectively a drug will perform in humans. Additionally, it helps identify the most effective route of administration, dosage, and potential side effects, all of which are crucial for determining the likelihood of success in clinical trials.

Our Available Routes of Administration: We offer a range of delivery methods tailored to your specific research needs, each selected based on the pharmacological profile of the drug being studied. These include:

  • Intraperitoneal (IP): Typically used for small-molecule drugs, this route provides rapid absorption into the bloodstream.
  • Intravenous (IV): Involves administering a substance directly into the bloodstream through a vein, typically the tail vein due to its accessibility.
  • Sub Cutaneous (SC): Subcutaneous delivery is a procedure that involves injecting fluid into a rodent through the skin. The most common injection site for rodents is the loose skin over the neck and shoulders.
  • Oral Gavage (OG): Oral gavage involves passage of a gavage needle into the esophagus to administer liquid compounds to the stomachs of rodents
  • Intracardiac (IC): A direct method for injecting substances into the heart, often used in certain animal models.
  • Hepatic Portal (HP): For compounds targeting liver metabolism, this method delivers drugs directly into the portal vein, mimicking a natural pathway for liver-centric therapies.
  • Hydrodynamic tail vein injections (HDTV): Designed for compounds requiring higher doses or formulations that need to be delivered in specialized vehicles.
    And additional routes customized for your specific research requirements.
  • Intra Articular (IA): A technique used to deliver substances directly into a joint space, typically for research involving arthritis, osteoarthritis, inflammatory joint diseases, or drug testing.

Metabolic Profiling and In-Depth Analysis

In addition to route selection, the metabolic fate of the compound in vivo is assessed with a high level of precision. Our state-of-the-art facility is equipped with metabolic cages, which allow for the continuous collection of biological samples, such as blood and tissues, under controlled conditions. These samples are then sent to your CRO of choice, or to one of our third party partners for analysis using Liquid Chromatography-Mass Spectrometry (LC-MS/MS), a powerful technique that enables us to measure trace levels of the drug and its metabolites with high sensitivity.

The key metabolic metrics evaluated include:

  • Plasma Concentration-Time Curve: This measures the concentration of the drug in the bloodstream over time, providing insights into its absorption, distribution, and elimination kinetics.
  • Clearance, Half-Life, and Volume of Distribution: These critical parameters describe how quickly the drug is eliminated from the body, how long it remains effective, and how extensively it disperses into tissues and organs.
  • Oral Bioavailability: By measuring the fraction of the drug that reaches the systemic circulation when taken orally, we assess its suitability for oral administration versus other methods.
  • Blood-Brain Barrier Penetration: For drugs targeting the central nervous system, this metric assesses the compound’s ability to cross the blood-brain barrier, a critical factor for neurological therapies.
  • Protein Binding: This indicates the extent to which the drug binds to plasma proteins, influencing its free (active) form and overall efficacy.
  • Routes of Metabolism and Identification of Metabolites: Understanding how the body processes the drug and which metabolites are produced is essential for evaluating potential toxicity and identifying the most active or harmful metabolites.

Supporting In Vivo Pharmacology and Drug Optimization

In vivo pharmacokinetic studies serve not only to understand how a drug behaves within the body but also to support in vivo pharmacology, which is crucial for assessing the therapeutic effects of a drug. By combining PK data with pharmacodynamic (PD) measurements—such as the drug's effect on biological systems—we can establish a robust correlation between drug concentration and its physiological outcomes. This helps researchers understand the relationship between the drug’s presence in the body and its functional response, providing valuable insights into its mechanism of action.

These PK/PD correlations are critical for identifying optimal dosing regimens, predicting clinical efficacy, and improving the overall design of the compound. Furthermore, they guide efforts to optimize drug properties by identifying areas for enhancement, such as improving bioavailability, extending half-life, or reducing toxicity. Through this iterative process of testing and optimization, we ensure that the compounds under development are as effective and safe as possible before moving into human clinical trials.

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