What Is Steady-State Concentration In GLP Toxicokinetic (tox) Study?

Glp toxicokinetic studies are involved in the evaluation of systemic exposure of the toxicity species to either the drugs or their metabolites. The data retrieved from these studies can later be used for establishing the correlation between the dose level findings and the non-clinical toxicology analysis.

Planning a GLP toxicity study program involves the early development of an appropriate plasma drug assay. Such assays are performed to comply with the principles of the good laboratory practises, exposure of the drug at their steady state concentrations, and effective collaboration amongst suitable professionals.

The relevant IND enabling studies assay should be developed and validated within the stipulated timeframe so that it can be rather utilised for the GLP toxicity studies of the investigational new drug. The pharmacokinetic professional ensures that the toxicology studies incorporates sufficient experimental data from the TK study so as to accomplish the program goals thereby accurately interpreting the experimental data generated.

The exposure assessments are accurately made at the steady state concentration levels rather than a single dose level. Such in vivo toxicology studies should be relatively performed under the regular considerations of the Good Laboratory Practise requirements.

When a drug is repeatedly administered to the subjects, it is important for the clinicians to evaluate the changing pharmacokinetic parameters, steady state concentrations, and accumulation potential of the drug. The results obtained from this assessment should be further correlated with the changes observed in their blood concentrations derived from the single dose study levels.

Whenever it becomes difficult to estimate the steady state drug concentration by performing a single-dose study under clinical conditions of the repeated administration of a drug, it is better to assume metabolic enzyme induction ability. The changing degree of the pharmacokinetic parameter should be evaluated depending on the administered dose and its dosing frequency. This evaluation should be worked out in conjunction with both the dose and dosing regimen intended for its clinical evaluation. On the basis of the results derived from the single dose studies, the appropriate number should be determined.

During the final dose administration, it is imperative to consider sufficient number of sampling time points. This aids in the evaluation of the drug elimination rate, its accumulation degree and linearity.

For a standard pharmacokinetic study, the clinician should include a sufficient number of data collection points as well as pharmacokinetic parameters. Such pharmacokinetic parameters are inclusive of minimum and maximum blood concentration, volume of distribution at steady state concentration of the drug, its half-life, and mean residence time.

Single trough screen method may be employed in the estimation of the steady state drug concentration after its repetitive drug administration by collecting one sample from each subject immediately prior to its next administration. This makes it easier for obtaining information regarding the distribution of the plasma drug concentration after a specific dose administration.

In the event of detection of an unexpectedly higher accumulation degree, the metabolic enzyme activity as well as toxicity of the drug-clearing organs are both considered as the causal factors. 

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