Tiêu đề 1. INTRODUCTION TO CLINICAL PHARMACOKINETICS.pdf ✅

PHARMD GURU Page 2 The three important pharmacokinetic parameters that describe the plasma level-time curve and useful in assessing the bioavailabilities of a drug from its formulation are: 1) PEAK PLASMA CONCENTRATION (Cmax): The point of maximum concentration of drug in plasma is called as the peak and the concentration of drug at peak is known as peak plasma concentration. 1) The peak represents the point of time when absorption rate equals elimination rate of drug. 2) It is also called as peak height concentration and maximum drug concentration. 3) It is expressed in mcg/ ml. 4) Peak concentration is often related to the intensity of pharmacologic response and should ideally be above minimum effective concentration (MEC) but less than the maximum safe concentration (MSC). 2) TIME OF PEAK CONCENTRATION (Tmax): The time for drug to reach peak concentration in plasma (after extravascular administration) is called as the time of peak concentration. It is expressed in hours. 3) AREA UNDER THE CURVE (AUC): It represents the total integrated area under the plasma level-time profile and expresses the total amount of drug that comes into the systemic circulation after its administration. AUC is expressed in mcg/ml X hours.

PHARMD GURU Page 4 RATE OF REACTION: The rate of a reaction or process is defined as the velocity at which it proceeds and can be described as either zero-order or first-order or mixed order. ZERO-ORDER REACTION:  The reaction proceeds at a constant rate and is independent of the concentration of drug present in the body.  Consider the rate of elimination of drug A from the body. If the amount of the drug A is decreasing at a constant rate, then it is written as: dA/dt= — K0 Where k0 is the zero-order rate constant. FIRST-ORDER REACTION:  The reaction proceeds at a rate that is dependent on the concentration of drug present in the body.  If the amount of drug A is decreasing at a rate that is proportional to A, the amount of drug A remaining in the body, then the rate of elimination of drug A can be described as: dA/dt= — KA Where “k” is the first-order rate constant. MIXED ORDER REACTION: Reaction that follows both first order and zero order reaction. COMPARTMENT MODELS:  Physiologic pharmacokinetic models are frequently used in describing drug distribution in animals, because tissue samples are easily available for assay.  On the other hand, tissue samples are often not available for human subjects, so most physiological models assume an average set of blood flow for individual subjects.  In contrast, because of the vast complexity of the body, drug kinetics in the body is frequently simplified to be represented by one or more compartments that communicate reversibly with each other.  A compartment is not a real physiologic or anatomic region but is considered as a tissue or group of tissues that have similar blood flow and drug affinity.