A pharmacology branch which deals with the behaviour and therapeutic effects of a drug candidate is called toxicology. At their average concentrations, human body accepts, absorbs, and eliminates drug. This ADME process of a drug is based on its affinity for different enzymes, receptors and the transporters. If the concentration is high enough, these transporters, enzymes and receptors achieve their limit of saturation. At this time, the behaviour and the effects produced by a drug are different.
Overview of the Toxicology Studies at a glance –
Here is some valuable information obtained from the toxicology studies –
- It produces and presents some useful data which further assists in developing a strategy for non-clinical processes. This data has a certain degree of influence on the strategy being developed for the clinical development process.
- Toxicology studies assess the gender differences, dose proportionalities, and drug exposure comparisons derived from both the single and multiple-dose studies.
- The Tk assay arm of a non-clinical tox study generally features lesser timepoints and fewer headcounts of subjects and endpoints in comparison to both the clinical and non-clinical pharmacokinetic studies.
- The half-life of a drug candidate is accurately determined in the tox studies as the blood samples collected for the concentration-time assessment are relatively less in the count.
Factors affecting the toxicology studies –
There is a wide array of factors involved in the determination of the toxicity potential of a drug candidate under analysis. Some of the key ones are –
Absorption of the drug substance –
There are various modes through which a drug is absorbed in the body. According to the research findings, the drugs that are absorbed through carrier-mediated or active transport mechanisms display a less degree of toxicity than those that are absorbed through the passive drug absorption mechanism.
Distribution factor of a drug –
Distribution of a drug adversely affects a drug’s toxicity profile. Those drugs that show a larger distribution volume tend to be more toxic than those are localized in their mechanism of action.
Biotransformation efficiency –
Most of the drugs require the support of enzymes to undergo metabolism. Such drugs exhibit a higher turnover and are usually determined to be less toxic than other drugs.
Nature of the metabolites –
Drugs that are converted into pharmacologically inactive molecules have a low toxicity profiling than those drugs which produces metabolites to exhibit their physiological effects.
Types of toxicity studies –
There are two critical types of toxicology studies widely performed in clinical development industries –
Single-dose toxicity studies –
Single-dose studies are those that are performed early in the phase of clinical development of a pharmaceutical entity. Such studies require the use of plasma for obtaining stability data for determining the characteristics of the analyte in the matrix. Alternatively, additional toxicokinetic studies may be needed once the single-dose studies are accomplished successfully.
Repeated-dose studies –
Here, both the pharmacokinetic and pharmacodynamic factors are taken into consideration for selection of both the treatment regimen and species.
Besides, the above two key types of toxicology studies, genotoxicity studies, carcinogenicity studies, reproductive toxicity studies are also performed to evaluate the toxicity profile of a drug candidate considering all possible toxicity parameters.