Clinical Pharmacology is the scientific discipline concerned with the interactions between medicinal products and the human organism. It connects fundamental pharmacological research with clinical application and provides the scientific basis for the rational development, dosing and use of medicinal products. In clinical development, Clinical Pharmacology encompasses all studies and analyses that characterise the behaviour of a medicinal product in the body (pharmacokinetics) and the effect of the medicinal product on the body (pharmacodynamics). These insights form the basis for dosing recommendations, the identification of patient populations at particular risk, and the regulatory assessment of a new active substance.
Pharmacokinetics and pharmacodynamics
Pharmacokinetics (PK) describes what the body does to the medicinal product – that is, the processes of absorption, distribution, metabolism and elimination (ADME). Important pharmacokinetic parameters include half-life, bioavailability, volume of distribution and clearance. Pharmacodynamics (PD), conversely, describes what the medicinal product does to the body – that is, the relationship between drug concentration and effect (e.g. receptor binding, biomarker changes, clinical effect). PK/PD modelling combines both perspectives and enables the simulation of dosing regimens before resource-intensive clinical trials are conducted. It is a central tool of modern clinical drug development.
Clinical pharmacology studies in development
Various types of clinical pharmacology studies are conducted during clinical development:
- First-in-human studies (Phase I): Initial administration to healthy volunteers or patients to characterise safety, tolerability and PK.
- Dose escalation studies: Stepwise increase of the dose to determine the maximum tolerated dose (MTD) and the therapeutic window.
- Bioavailability and bioequivalence studies: Comparison of different formulations or routes of administration with regard to their PK profiles.
- Drug-Drug Interaction studies (DDI): Investigation of interactions with other medicinal products, particularly via CYP enzymes and transporter proteins.
- Special population studies: PK studies in patients with impaired renal or hepatic function, in elderly patients, or in children (paediatric PK).
The results of these studies feed directly into the product information (Summary of Product Characteristics, Package Leaflet) and determine the approved dosing for different patient groups.
Regulatory requirements
ICH guidelines E4, E7 and M9, together with the EMA guideline on the investigation of drug interactions, define the regulatory requirements for clinical pharmacology investigations as part of marketing authorisation applications. For a Marketing Authorisation Application (MAA), the EMA expects a complete characterisation of the PK profile of the investigational substance, including the influence of intrinsic factors (age, weight, renal and hepatic function, genetic polymorphisms) and extrinsic factors (food, concomitant medication, CYP inducers and inhibitors). The corresponding clinical pharmacology study data are summarised in the Common Technical Document (CTD) in Module 2.7.1 (biopharmaceutic studies) and Module 2.7.2 (clinical pharmacology studies), and are assessed in detail by regulators during Scientific Advice and the marketing authorisation procedure. For biologics and biosimilars, extended requirements apply: in addition to classic PK characterisation, immunogenicity studies and demonstration of PK similarity to the reference product are mandatory components of the marketing authorisation dossier. Model-based approaches such as Model-Informed Drug Development (MIDD) are increasingly recognised by the EMA and FDA as a regulatorily acceptable tool for dose finding and for deriving recommendations for subpopulations.
Relevance for clinical trials
Clinical Pharmacology is the scientific foundation for all subsequent clinical development phases. A sound PK/PD understanding derived from early studies enables rational dose finding, reduces the risk of costly failures in Phase II and III, and provides the scientific arguments for regulatory assessment. Population pharmacokinetic models also allow dosing recommendations to be derived for patient groups that were underrepresented in pivotal trials – including children, elderly patients, or individuals with renal and hepatic impairment. Trials lacking adequate clinical pharmacology characterisation frequently receive conditions or restricted approvals from regulators, for example excluding certain patient groups from the approved indication. Full-service CROs such as mediconomics support sponsors in the planning and conduct of clinical pharmacology studies, integrated PK/PD modelling, and the regulatorily compliant preparation of clinical pharmacology dossiers for MAA and NDA submissions.
Frequently Asked Questions (FAQ)
What is the difference between pharmacokinetics and pharmacodynamics?
Pharmacokinetics (PK) describes how the body absorbs, distributes, metabolises and excretes a medicinal product – that is, what the body does to the medicine. Pharmacodynamics (PD) describes the effect of the medicinal product on the body – that is, what the medicine does to the body. In modern drug development, PK and PD are combined in integrated PK/PD models to quantitatively describe the relationship between dose, concentration and effect.
Why are Drug-Drug Interaction studies important?
Many patients take several medicinal products concurrently. Interactions between medicinal products can increase the concentration of an active substance (thereby causing toxicity) or decrease it (thereby reducing efficacy). DDI studies identify such risks at an early stage and enable dose adjustments or contraindications in the product information. Regulators require comprehensive DDI characterisation for all new medicinal products.
When are studies in special populations conducted?
Studies in special patient groups – such as patients with renal or hepatic impairment, elderly patients or children – are generally conducted in Phase I or early Phase II, before the pivotal efficacy trials begin. They are required because the PK of these groups can differ substantially from that of a healthy adult. Without this data, the marketing authorisation would typically be granted with restrictions, or use in these populations would be excluded.
Regulatory references
- ICH E4: Dose-Response Information to Support Drug Registration
- ICH E7: Studies in Support of Special Populations: Geriatrics
- ICH M9: Biopharmaceutics Classification System-Based Biowaivers
- EMA Guideline on the investigation of drug interactions (2012)
- FDA Guidance for Industry: Clinical Pharmacology Considerations for Human Immunodeficiency Virus (HIV) Drug Combination Products (2019)