Pharmacokinetics is the study of what happens to drugs in the body, which encompasses the processes of drug absorption, distribution, metabolism, and elimination. Non-Compartmental Analysis, also known by its acronym NCA, is a simple and descriptive methodology used to understand the pharmacokinetic properties of a drug. It is an a posteriori analysis in that pharmacokinetic metrics are determined using actual data (e.g., measured serial drug concentrations over time in a clinical study). The NCA methodology assumes that the body behaves like a single compartment and does not make assumptions about hypothetical body compartments. This means that the drug is distributed evenly throughout the body with no difference in the rate of elimination from different organs.
The NCA methods generally involve the use of algebraic equations to estimate pharmacokinetic metrics that are used to help describe a drug’s absorption, distribution, metabolism and elimination from the body. The common pharmacokinetic metrics obtained from a NCA include, but are not limited to, are the maximum drug concentration achieved (Cmax), time to reach the maximum drug achieved (Tmax), area under the concentration-time curve (AUC), terminal elimination half-life (t1/2), trough concentration (Ctrough) and clearance (CL).
Cmax. Cmax is the maximum drug concentration achieved in a specified matrix, such as blood or plasma, after a drug has been administered before a second/subsequent dose. The numerical value of Cmax does not describe anything related to the distribution of the drug, where, the drug concentration may be significantly different in certain organs. The Cmax following an intravenous dose of drug is dependent on the study protocol. Whilst, the Cmax following an extravenous dose of drug is dependent on the extent and rate of drug absorption and disposition. The magnitude of Cmax is often considered when it is near the upper therapeutic limit as this is when potential adverse events may occur.
Tmax. Tmax is the time taken to achieve Cmax after a drug has been administered. Tmax is governed by the rate of drug absorption and elimination and occurs when the rate of absorption is equal to the rate of elimination. The value of Tmax may be of clinical interest when the time to effect is driven by Cmax.
AUC. The AUC is a measure of the total drug exposure in the body over time. AUC is a key pharmacokinetic metric for evaluating drug efficacy and safety as it provides insight into the extent of drug exposure and rate of clearance from the body. The AUC value may be used in the therapeutic drug monitoring of drugs with a narrow therapeutic window, or when wanting to determine whether two formulations of the same drug provide the same drug exposure.
t1/2. The t1/2 is the time it takes for the concentration or amount of drug in the body to reduce by exactly one-half (50%). It provides insight into the duration of action for a drug and may be used to guide dosing regimens/schedules. For instance, for a drug with a short half-life, the drug may be administered more frequently in order to maintain a therapeutic concentration required for an effect. Rather, for a drug with a long half-life, the drug may be given less frequently.
Ctrough. Ctrough is the concentration achieved in a specified matrix immediately prior to the administration of a subsequent dose. The Ctrough may be considered in clinical practice to ensure that concentrations are above the minimum concentration limit to ensure therapeutic efficacy. The Ctrough may be different to Cmin which is the minimum concentration achieved during the interval of two drug doses being administered.
CL. Clearance describes the ability of the body to eliminate a substance, such as a drug, from the body without identifying the specific underlying removal mechanisms. It is defined as the volume of a specified matrix (e.g. plasma) from which a substance is completely removed per unit time. Clearance is important as it is used to guide dosing regimens in order to achieve a specific drug concentration.