Finding a molecule that works against a disease target is only one part of developing a new medicine. Researchers need to understand how that drug interacts in the human body, how much of the drug enters the bloodstream and tissues, how long it is active, and how it is eliminated. This is where pharmacokinetics (PK) comes into play.

Pharmacokinetics is what happens to a drug in the body over time. The discipline is often summarized as ADME-absorption, distribution, metabolism, and excretion. PK plays a key role in instructing researchers on drug candidate selection, dosing, formulation, safety, and efficacy from the early drug discovery stage, through clinical trials and the regulatory review process.

Understanding ADME: The Foundation of Pharmacokinetics

ADME consists of four components that describe the behavior of drugs.

Absorption describes the passage of a drug into the systemic circulation. Solubility, permeability, gastrointestinal conditions, food, and formulation can all affect absorption of oral medicines.

Distribution refers to the distribution of the drug from the bloodstream to the tissues and organs. Blood flow, tissue permeability, protein binding, and drug-specific characteristics influence its distribution.

Metabolism is the process of altering the drug. This is usually done by enzymes in the liver, but sometimes in other tissues. Metabolism can deactivate a drug, activate a prodrug, or form metabolites that are biologically active themselves.

Excretion is the procedure by which the drug and its metabolites are eliminated from the body. Most drugs are eliminated by the kidneys, but some drugs are eliminated in the bile and in the faeces.

They are responsible for important pharmacokinetics (PK) parameters such as Cmax, Tmax, AUC, clearance, volume of distribution, and half-life. These measurements provide information that informs dosing frequency, formulation, efficacy, and safety.

Pharmacokinetics in Drug Discovery

The real story on PK begins well before human clinical trials. A compound can be excellently active in laboratory experiments but still be unsuccessful as a drug because it is poorly absorbed, rapidly metabolized, cleared too quickly, or cannot reach the necessary tissues.

That's why when pharmaceutical researchers select candidates, they consider ADME properties along with pharmacological activity. Lab studies, animal experiments, computational tools and PK models can help to identify compounds with a better chance of being successful in development.

This process has been aided by modern physiologically based pharmacokinetic (PBPK) modelling, which enables investigators to simulate drug behavior based on drug-specific properties and physiological information. PBPK models have been shown to have applications in candidate selection, prediction of human PK, formulation development and assessment of drug-drug interactions. This means PK can help identify problems earlier, and thus reduce the risk of taking unsuitable compounds into expensive clinical studies.

From Preclinical Studies to First-in-Human Trials

One of the most important uses of PK is to help researchers determine appropriate doses for initial human studies. Developers are able to estimate the possible human exposure to the drug before a drug is given to humans by combining information from animal PK studies, toxicology, in vitro experiments, metabolism studies, and pharmacology.

PBPK models can assist in combining these sources of information and predicting how a compound might behave in humans. FDA considers PBPK modelling a useful instrument for addressing questions of human exposure, drug-drug interactions, organ impairment and other factors affecting drug disposition.

There is also current research into combining PBPK with artificial intelligence and machine learning. In 2026, a study of 40 small molecules that reached clinical development at Roche between 2003 and 2024 compared conventional PBPK, high-throughput PBPK, and machine-learning approaches to predict clinical PK. This research reflects a growing interest in the integration of mechanistic modelling and data-driven methodologies.

The Role of PK in Clinical Trials

PK is critical in determining how the medicine should be given when a drug reaches clinical development. Early phase studies look at how the exposure to the drug changes with dose. Parameters such as Cmax, AUC, and half-life are assessed to determine if the extent of exposure increases linearly with dose and if the drug accumulates after repeated administration.

For example, a drug with a long half-life may permit once-daily or less frequent dosing, whereas a drug that is eliminated rapidly may require more frequent administration or a modified-release formulation. PKPD modelling can also incorporate PK with pharmacodynamic data. This enables researchers to study the relationship between drug exposure and biological or clinical response.

Population Pharmacokinetics and Patient Variability

Not all patients metabolize drugs the same way. Age, body weight, kidney function, liver function, genetics, disease status and other medicines can affect drug exposure. PopPK (population pharmacokinetics) enables researchers to understand these differences by analyzing PK data from groups of patients. PopPK can be of particular use in the development of medicines for children, the elderly and those with renal or hepatic impairment.

The FDA understands the importance of population PK as a means of comprehending variability and informing individualized dosing. In some cases, appropriate PopPK analyses can also reduce the need for additional clinical studies.

For instance, pharmacometric approaches have been used to simulate virtual populations of patients and to estimate the likelihood that proposed pediatric doses will lead to appropriate exposure across different age groups.

PBPK and Drug-Drug Interactions

Specifically, PBPK has become a powerful tool for the assessment of drug-drug interactions (DDIs). For example, when two medicines are taken together, one may inhibit or induce enzymes or transporters responsible for the metabolism or movement of the other. This may result in increased or decreased exposure and may affect safety or efficacy.

PBPK models can also simulate these interactions and help determine whether clinical studies are needed and what doses may be appropriate. Drug development and regulatory submissions, particularly in the assessment of enzyme and transporter-mediated interactions, have increasingly seen the incorporation of PBPK analyses by regulatory agencies such as the FDA.

Pharmacokinetics of Biologics

The growth of biologic medicines has posed additional challenges for pharmacokinetic analysis.