Introduction to Basic Pharmacokinetics

-110104 김라온

Pharmacokinetics is the study of how drugs are absorbed, distributed, metabolized, and excreted in the body. The term originates from Greek, combining pharmacon, meaning "drug," and kineticos, meaning "movement." A key concept in pharmacokinetics is that the concentration of a drug changes over time, which explains how the drug moves within the body. The variation in concentration is influenced by the responses of biological organs and tissues to the administered drug. This underscores the fact that drug molecules do not operate in isolation; instead, it is the interaction between these molecules and the biological systems that modulates their concentration levels.

Pharmacokinetics and pharmacodynamics are distinct concepts: pharmacokinetics deals with "the bodys action on the drug," while pharmacodynamics focuses on "the drugs action on the body." It is essential to differentiate between these two concepts for predicting drug effects and determining appropriate dosages. In the past, pharmacokinetics was sometimes translated as "drug dynamics," which led to confusion. In Japan, pharmacokinetics is translated as "drug disposition," which conveys a similar meaning.

In the drug development process, pharmacokinetics plays a crucial role in decision-making at various stages and is essential for finding the appropriate dosage to achieve the desired therapeutic effect. Measuring drug efficacy in actual patients is challenging, so it is necessary to utilize the relationship between pharmacokinetics and pharmacodynamics to select suitable dosing regimens. ADME refers to the four major processes of pharmacokinetics: Absorption, Distribution, Metabolism, and Excretion. The general pharmacokinetic model describes how a drug is linearly absorbed into the body after oral administration, distributed to tissues outside the blood vessels, and removed from the body in a linear manner.

In the absorption process, when a drug enters the gastrointestinal tract, it is broken down and dissolved in digestive fluids, then passes through the intestinal epithelial cells. The first-order absorption rate constant (ka) indicates how quickly a drug is absorbed, and the importance of its properties cannot be overlooked. Once absorbed, the drug is distributed throughout the body via the bloodstream, which implies the process of diffusion into tissues outside the blood vessels. After metabolism, the drug is excreted via bile or urine, with clearance (CL) playing a significant role in this process. Clearance (CL) is defined as the volume of plasma or blood from which a drug is completely removed per unit time, remaining a fixed value independent of drug concentration. The half-life of a drug is the time it takes for its concentration to decrease by half, determined by clearance (CL) and volume of distribution (Vd).

Pharmacokinetic parameters exhibit variability across different medications, with the values of these parameters influenced by individual physical characteristics. For example, in elderly patients with diminished renal function, the clearance (CL) rate may be significantly lower. Furthermore, there is a general correlation between body weight and pharmacokinetic behavior, which must be considered when evaluating drug disposition. an increase in volume of distribution (Vd). In multiple dosing scenarios, when a drug is administered repeatedly before it is completely eliminated, the plasma drug concentration is maintained within a certain range. To reach a steady state, the dosing interval must be 4 to 5 times the half-life. Non-linear pharmacokinetics refers to situations where clearance (CL) is not constant and the rate of elimination varies with drug concentration, shifting to non-linear kinetics as the concentration approaches Km.

Finally, only unbound drugs can bind to their targets, and a lower plasma protein binding rate is generally considered advantageous. However, this is influenced by various pharmacokinetic parameters. Such foundational theories play a vital role in understanding drug efficacy and safety, as well as in drug development and clinical application.