What is Toxicokinetics (TK) Study?
Toxicokinetics is merely a pharmacokinetic study of the drug when administered at quantities much higher than the therapeutic dose to evaluate the toxic level of the drug. Toxicokinetics is thus the appropriate term for the study of the kinetics of all substances at toxic dose or exposure levels. During GLP toxicology study by FDA standards, the body reaches the absolute limit to cope with the impact of the drug to the point of toxicity. Understanding the dosage of the drug during the toxicokinetic study is essential as this aspect defines the difference in a drug being therapeutic vs. toxic. The same drug given in a small dose may start healing at the site of action. But, when administered in a high dose, it can even be fatal for the human body.The reason behind the popularity of Toxicokinetics lies in the study’s ability to provide insights on molecules’ systemic exposure and related adverse effects. This is an especially important consideration for the cardiovascular system, the central nervous system, and respiratory assessments. Further, single-dose studies carried under this analysis assist in predicting the duration and rate of exposure at the time of one dosing interval. This is benchmark information providing the right dose levels for later stages of the study.Overall, the data obtained from toxicokinetic study assesses the toxic responses of various drug compounds. The result of this study becomes the basis for knowing the right dose of a new drug safe for the human body. Moreover, the study also provides insights into how certain medications can diversely affect people of different ages, genders, and ethnicities.
What are the various steps in a Toxicokinetics (TK) Study?
Toxicokinetics is essentially the study that helps in understanding how a substance enters the body and what happens to it inside the body. The term “disposition” is often used in place of toxicokinetics to describe how the body disposes of the drug over time.
Many factors impact toxicokinetics but here are the four most prominent underlying processes, namely absorption, distribution, metabolism, and elimination, in a TK analysis like PK analysis. These stages or processes assist in understanding how the body reacts and interacts with the administered drugs.
Absorption
Absorption, the first step of a toxicokinetic study, is the process of a substance entering the blood circulation. Whenever a toxin is administered to the body, it crosses a membrane to enter the systemic circulation in a process known as absorption. These toxins are absorbed into the body through various channels such as intestine, lungs, skin, etc. Every toxin is absorbed in the human body differently. While some are difficult or hardly get absorbed, others enter rather quickly. Generally, the form of a toxin directly affects the ease of it being absorbed in the human body. For example, a toxin in gas form may be easily absorbed through lungs within minutes, while when prepared for oral consumption may take hours.
Distribution
Distribution describes the reversible transfer of drug within the body from one location to another. The distribution of a drug is affected by multiple factors including lipid-solubility, concentration in plasma and various tissues, and binding to plasma proteins, transport proteins, and tissues.
Metabolism
Metabolism is an irreversible process by which a drug is converted to other chemical entity (metabolite). Metabolism happens primarily in the liver. At the time of metabolism, the xenobiotic chemicals administered by the body are altered with the help of non-enzymatic or enzymatic reactions. The aim is the conversion of lipophilic compounds, which are poorly excreted, to the entities that can quickly be discharged from the body. If metabolism fails to convert these compounds, toxic reactions may follow.
Elimination
The drug chemicals are excreted from the system either as water-soluble metabolites or in their unchanged form. While the kidney plays an essential role in excreting water-soluble toxins from the body, excretion of other compounds needs the help of the biliary system, liver, etc.
Which TK Assay does NorthEast BioLab Offer during Drug Discovery and Preclinical Phases?
We offer a wide range of TK Assay during the early discovery phase when a potential drug (NCE) is evaluated for ADME properties. Once an NCE is found suitable for further development, we also provide IND enabling Tox studies in animals. TK Assay in animals are critical for advancing the drug into the clinical phase. Toxicokinetic studies are run in various animal species depending on the therapeutic area and the most appropriate animal model. In general, toxicokinetic studies are conducted in at least two animal species. We develop fully validated bioanalytical methods for GLP toxicology studies in various biological matrices of all animal species.
Why choose NorthEast BioLab for your Toxicokinetics (TK) Study?
We, at NorthEast BioLab, would assist with your challenging toxicokinetic studies. Since the TK analysis is a vital component of drug development, expert guidance during the end-to-end process is imperative. Knowing the toxicity of a drug compound helps the scientists decide the correct drug dosage to be used in early clinical trials and development. Hence, carrying out the GLP toxicology studies utilizing a fully validated and reliable bioanalytical method is necessary.
While the TK study may be a lot like PK analysis, the difference in multiple aspects and evaluation is considerably high. As TK analysis helps mitigate or uncover the risks associated with a drug compound, we would ensure that the absolute integrity of your data and processes is maintained throughout.