Pharmacometrics (PMx), Pharmacokinetics, Pharmacodynamics (PK/PD)

Regulatory agencies are responsible for approving all new drugs and for ensuring that all available drugs on the market are effective and safe for human use. Understanding the safety and effectiveness of any drug depends, in large part, on pharmacokinetics (PK), pharmacodynamics (PD), and pharmacometrics (PMx). PK, PD, and pharmacometric modeling and simulation approaches such as population PK (popPK) analyses are used to understand the characteristics of drugs and how they behave in different patient populations.

Pharmacokinetics vs. Pharmacodynamics

The difference between pharmacokinetics (PK) and pharmacodynamics (PD) is that pharmacokinetics is the movement of drugs through the body, whereas pharmacodynamics is the body’s biological response to drugs. In the simplest terms, pharmacokinetics is what the body does to the drug and pharmacodynamics is what the drug does to the body.

PK describes a drug’s absorption, distribution, metabolism, and excretion properties (known as ADME) and PD describes how biological processes in the body respond to or are impacted by a drug. While PK describes a drug’s exposure by characterizing its ADME properties and bioavailability as a function of time, PD describes a drug’s response in terms of biochemical or molecular interactions. PK/PD together can be thought of as an exposure/response relationship.

Understanding the exposure-response relationship (PK/PD) is key to the development and approval of every drug. PK and PD data contribute to about 25% of what is in a drug package insert or drug label. Strategic planning of the overall drug development program and an intelligent pharmacokinetic study design can accelerate the development process to help ensure safety and efficacy endpoints are achievable.

Pharmacometrics, Pharmacokinetics, and Pharmacodynamics Services:

• Data Management, Programming, and CDISC Dataset Creation
• Noncompartmental PK Analysis (NCA)
• Population Pharmacokinetics (popPK)
• Analysis Plans
• Dosing Simulations
• Comprehensive Submission-Ready Packages for Regulatory Authorities
• Designing and Interpreting Nonclinical and Clinical ADME Studies
• Bioanalytical Method Validation, Reports, and Compendial Analytical Methods

The Importance of PK/PD Analyses

PK/PD analyses are important because they help us understand how drugs behave in the body and how the body reacts to drugs, respectively. Drug developers use insights gained from PK and PD analyses to design better clinical studies (i.e., what dose to use or how different drugs interact with each other in the body). Clinicians use the information from PK and PD analyses (as presented in the drug label or package insert) to treat different types of patients (e.g., patients with and without renal impairment or elderly versus younger patients). PK/PD analyses and PK/PD modeling can be used to determine a number of important drug development parameters related to clinical study design.

PK and PD Analyses can be used to:

• Characterize drug exposure
• Determine an appropriate dose for a clinical study
• Assess changes in dose requirements
• Estimate the rate of elimination and absorption
• Assess relative bioavailability/bioequivalence
• Characterize intra- and inter-subject variability
• Understand concentration-effect relationships
• Establish safety margins and efficacy characteristics