Tiêu đề 1. INTRODUCTION TO CLINICAL PHARMACOKINETICS.pdf ✅

PHARMD GURU Page 1 PHARMACOKINETICS: Pharmacokinetics is defined as the kinetics of drug absorption, distribution, metabolism, excretion (ADME) and their relationship with the pharmacologic, therapeutic or toxicological response in man and animals. CLINICAL PHARMACOKINETICS: The applications of pharmacokinetic principles in the safe and effective management of individual patient are called as clinical pharmacokinetics. 1) Clinical pharmacokinetics is the application of pharmacokinetic methods to drug therapy. 2) It involves a multidisciplinary approach to individually optimized dosing strategies based on the patient's disease state and patient-specific considerations. 3) Pharmacokinetics is also applied to therapeutic drug monitoring (TDM) for very potent drugs such as those with a narrow therapeutic range, in order to optimize efficacy and to prevent any adverse toxicity. For these drugs, it is necessary to monitor the patient, either by monitoring plasma drug concentrations (e.g., theophylline) or by monitoring a specific Pharmacodynamic endpoint such as prothrombin clotting time (e.g., warfarin). 4) The influence of many diseases on drug disposition is not adequately studied. Age, gender, genetic and ethnic differences can also result in pharmacokinetic differences that may affect the outcome of drug therapy. POPULATION PHARMACOKINETICS: Study of pharmacokinetic differences of drugs in various population groups is termed population pharmacokinetics. PLASMA DRUG CONCENTRATION-TIME PROFILE:  A direct relationship exists between the concentration of drug at the site of action and the concentration of drug in plasma.  A typical plasma drug concentration-time curve is obtained as follows: INTRODUCTION TO CLINICAL PHARMACOKINETICS
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 3 VARIOUS PHARMACODYNAMIC PARAMETERS ARE: MINIMUM EFFECTIVE CONCENTRATION (MEC):  It is defined as the minimum concentration of drug in plasma required to produce the therapeutic effect.  In case of antibiotics, the term minimum inhibitory concentration (MIC) is used.  It describes the minimum concentration of antibiotic in plasma required to kill or inhibit the growth of microorganisms. MAXIMUM SAFE CONCENTRATION (MSC):  It is also called as minimum toxic concentration (MTC), it is the concentration of drug in plasma above which adverse or unwanted effects are precipitated.  Concentration of drug above MSC is said to be in the toxic level. SUB-THERAPEUTIC LEVEL: The concentration of drug below MEC is said to be in the sub-therapeutic level. ONSET OF ACTION: The beginning of pharmacologic response is called as onset of action. It occurs when the plasma dreg concentration just exceeds the required MEC. ONSET TIME: It is the time required for the drug to start producing pharmacologic response. It corresponds to the time for the plasma concentration to reach MEC after administration of drug. DURATION OF ACTION: The time period for which the plasma concentration of drug remains above the MEC level is called as duration of drug action. INTENSITY OF ACTION: It is the maximum pharmacologic response produced by the peak plasma concentration of drug. It is also called as peak response. THERAPEUTIC RANGE: The concentration of drug between MEC and MSC represents the therapeutic range.
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.