Every drug development process involves a lot of research to test the compound for efficacy, safety, and toxicity. Multiple types of data, both in vivo and in vitro, are studied and forwarded to the clinics for the later developmental phase. This is where pharmacokinetics plays a vital role.
What Is The Role Of Pharmacokinetics In Drug Development?
Simply defined, it is the study of the kinetics of a drug or the associated metabolites in the body of an organism. There are four basic processes – absorption, distribution, metabolism, and excretion of a drug compound’s lifecycle.
How Does A Pharmacokinetics Study Analysis Works?
There are two basic approaches to pharmacokinetic study that involves compartmental analysis and non-compartmental analysis.
The non-compartmental analysis is concerned with the effects of exposure to the drug components and the elimination of the same. The advantage that lies here is that comprehensive PK information is not necessary for this analysis.
It involves components like the parameters of the concentration-time curve as well as the calculation of maximum exposure (Cmax). The log-linear slope from the concentration-time curve aids with the estimation of the terminal rate constant, half-life, and first-order elimination.
The compartmental analysis does require a comprehensive set of PK information. It involves mathematical models that signify hypothetical volumes for studying distribution and elimination of drug components. These mathematical models may incorporate zero-order kinetic methods, first-order kinetic processes, or the Michaelis-Menten Kinetics.
A simple example would be the introduction of the drug through intravenous bolus injection into one such mathematically determined compartment. Compartmental studies are either implemented at the early stages for initial assumption or in the later stages for population-based study. This is known as Pop PK. Such a model would take into consideration a rich and dense sampling for population-based data.
Several other covariates are also considered besides the rich samples but mostly from patients. These covariates include concomitant medications, the status of the disease, genotypes, and even race.
The Non-Clinical Approach & Use
The non-clinical approach does involve data generated from toxicokinetics tests; these are conducted in animals and way before the drug is introduced in human subjects. Cell lines are used here to test for drug route and efficacy.
Regulatory agencies conduct these studies as a part of their routine studies but these are also used for designing FIH study for drug development purposes. The dosage of drugs and their concentration-time aspects are also taken into account here. The non-observed adverse level effect of drugs is also a part of these pk assay. This is conducted within a safety range in highly sensitive animals.
With the evolution of advanced techniques like physiological based pharmacokinetic modeling and species based scaling methods. 10% of the drug components circulating in animals are taken into account for further studies in toxicology screening, which is vital to study bioactivity of the components in humans.
Pharmacokinetics forms the basis of drug development. The processes involved give detailed data on how a drug performs when incorporated in humans. It involves studies in animals, and the data generated is then forwarded for human studies.