Toxokinetics Analysis Service
Toxokinetics, which is also called ADME, can study the process of absorption, distribution, metabolism and excretion of exogenous chemicals in the body. ADME is part of the design of non-clinical trials. It plays an important role in understanding toxicity study results and comparing them with clinical data to evaluate human safety. The emphasis of the study is to interpret the toxicity assay results and improve the value of safety evaluation data. The purpose of toxokinetics study is to know the whole body exposure degree and duration under different dose levels of the selected drugs in the toxicity assay, predicting the potential risk of the selected drugs exposed to human body. The dosage of repeated administration toxicity assay is applied in ADME to study the dynamic change rule of drugs in vivo, obtaining pharmacokinetics data. If appropriate parameters are determined in ADME study, the repeated administration toxicity assay can be avoided.
Creative Biolabs has carried out the toxokinetics analysis service in accordance with relevant laws and regulations.
The process of toxokinetics analysis service:
- Design the drug administration protocol for toxokinetics.
- The design of drug administration protocol for toxokinetics assay should be based on the study protocol of toxicity assay, including dose, route, species selection, frequency and cycle of drug administration.
- To achieve maximum exposure to toxicity, the exposure degree of the drugs and its metabolites at high dose levels should be assessed.
- In some cases, a non-clinical trial conducts with a different method of administration (like different route of administration, different formulations) than the clinically intended drug. The systemic exposure should be evaluated based on the amount of exposure.
- Collect the samples according to the frequency required by exposure evaluation.
- The sampling time should be as close as possible to the frequency required for exposure evaluation. However, it should not be too frequent to avoid interfering with the normal conduct of toxicity test and causing excessive physiological stress response in animals.
- It is necessary to consider whether samples should be collected from all experimental animals or from a representative subgroup or satellite group.
- Analyze analytes and biological matrices (biological fluids or tissues).
- Data statistics and evaluation.
- Exposure evaluation data should be representative.
- If a data conversion has taken place, a reason should be given.
- Write experimental report according to complete toxokinetics data.
- The complete toxokinetics data should include the self-evaluation of the results and the relevant interpretation of the toxicity reaction.
- In the analysis of toxokinetics results, the exposure amount should be compared and used to evaluate the safe range of the tested drug.
We provide but are not limited to:
- To elaborate the relationship between the systemic exposure of the drugs and its metabolites and the dose and time of toxicity reaction.
- To evaluate the toxicity reaction of the drugs and its metabolites in different animal species, sex, age and organism state (like pregnancy state).
- To evaluate the rationality of species selection and drug regimen for non-clinical toxicity studies.
- To improve the predictive value of animal toxicity assay results for clinical safety evaluation. The evaluation of target site toxicity (like liver and kidney toxicity) due to accumulation of the selected drugs based on exposure is helpful to provide quantified safety information for subsequent safety evaluation.
- Combined efficacy and its exposure with toxicity and its exposure information to guide human trial design, such as initial dose and safety range evaluation. According to the degree of exposure, the results can guide clinical safety monitoring.
Exposure assessment services:
- Plasma protein binding.
- Tissue uptake experiment.
- Study on receptor properties.
- Immunogenicity and toxicology effects.
- Study on the pharmacological activity of metabolites.
- Study on species differences of metabolic characteristics.
References
- Punt A. Toxicokinetics in Risk Evaluations. Chem Res Toxicol. 2018,31(5):285‐286.
- Exley C, et al. Aluminum toxicokinetics. J Toxicol Environ Health. 1996,48(6):569‐584.
*For Research Use Only. Not for use in diagnostic procedures.