Basic Concepts and Terminology
Some of the basic concepts and terminology used in PK/PD are as follows:
Dose: The amount of drug administered to a patient.
Concentration: The amount of drug per unit volume of a biological fluid, such as plasma, blood, or urine.
Exposure: The extent to which the drug reaches the systemic circulation or the target site.
Bioavailability: The fraction of the administered dose that reaches the systemic circulation.
Clearance: The volume of biological fluid from which the drug is completely removed per unit time.
Volume of distribution: The apparent volume in which the drug is distributed in the body.
Half-life: The time required for the concentration or amount of drug in the body to decrease by 50%.
Effect: The change in a physiological or biochemical parameter caused by the drug.
Efficacy: The maximum effect that can be achieved by a drug.
Potency: The concentration or dose of a drug that produces 50% of its maximum effect.
Safety: The margin between the therapeutic and toxic effects of a drug.
Therapeutic window: The range of concentrations or doses that produce therapeutic effects without unacceptable toxicity.
Exposure and Response after a Single Dose
The PK/PD relationship after a single dose of a drug can be described by various models and equations. Some of the common models are as follows:
One-compartment model: A simple model that assumes that the body behaves as a single homogeneous compartment in which the drug is uniformly distributed and eliminated. The concentration-time profile after an intravenous bolus dose follows an exponential decay function. The elimination rate constant, clearance, volume of distribution, and half-life can be calculated from this model.
Two-compartment model: A more realistic model that assumes that the body consists of two compartments: a central compartment that includes the plasma and highly perfused organs, and a peripheral compartment that includes less perfused tissues. The concentration-time profile after an intravenous bolus dose shows a biphasic pattern, with an initial rapid distribution phase followed by a slower elimination phase. The distribution rate constants, intercompartmental clearances, volumes of distribution, and half-lives can be calculated from this model.
Multi-compartment model: A complex model that assumes that the body consists of more than two compartments, each with its own rate constants and volumes. This model can account for multiple peaks and troughs in the concentration-time profile after an intravenous bolus dose. However, this model is difficult to apply in clinical practice due to its mathematical complexity and parameter estimation.
Non-compartmental model: A model-free approach that does not assume any specific structure or mechanism for the body. This approach uses statistical methods to calculate PK parameters such as area under the curve (AUC), mean residence time (MRT), clearance, and volume of distribution at steady state (Vss) from the observed concentration-time data.
The PD relationship after a single dose of a drug can be described by various models and equations. Some of the common models are as follows:
Emax model: A simple model that assumes that the effect of a drug is directly proportional to its concentration at the receptor site, and that there is a maximum effect that can be achieved by the drug. The effect-concentration relationship follows a hyperbolic function. The Emax, EC50, and Hill coefficient can be calculated from this model.
Sigmoid Emax model: A more realistic model that assumes that the effect of a drug is not linearly related to its concentration at the receptor site, but rather follows a sigmoidal function. This model can account for the delay and hysteresis in the effect-concentration relationship. The Emax, EC50, and Hill coefficient can be calculated from this model.
Inhibitory Emax model: A model that assumes that the effect of a drug is inversely proportional to its concentration at the receptor site, and that there is a minimum effect that can be achieved by the drug. The effect-concentration relationship follows a hyperbolic function. The E0, Emax, IC50, and Hill coefficient can be calculated from this model.
Indirect response model: A model that assumes that the effect of a drug is not mediated by its direct interaction with the receptor site, but rather by its influence on a physiological or biochemical mediator that controls the effect. The effect-concentration relationship follows a differential equation. The baseline effect, rate constants, and feedback factors can be calculated from this model.
Therapeutic Regimens
The PK/PD relationship after multiple doses or continuous infusion of a drug can be described by various models and equations. Some of the common models are as follows:
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Superposition principle: A simple method that assumes that the concentration-time profile after multiple doses or continuous infusion of a drug is the sum of the concentration-time profiles after each individual dose or infusion. This method can be used to calculate the peak, trough, average, and fluctuation of the concentration after multiple doses or continuous infusion of a drug.
Steady state: A condition that occurs when the rate of drug input equals the rate of drug output, resulting in constant concentration and effect of the drug. This condition can be achieved after multiple doses or continuous infusion of a drug, depending on the dosing interval and half-life of the drug. The time to reach steady state, the steady state concentration, and the accumulation ratio can be calculated from this condition.
Loading dose: A large initial dose given to rapidly achieve a target concentration or effect of a drug. This dose can be followed by smaller maintenance doses to maintain the target concentration or effect. The loading dose and maintenance dose can be calculated from the PK/PD parameters of the drug.
Dose adjustment: A modification of the dose or dosing interval of a drug to achieve a desired concentration or effect of the drug. This modification can be based on various factors such as patient characteristics, disease state, concomitant medications, genetic variations, and therapeutic drug monitoring. The adjusted dose or dosing interval can be calculated from the PK/PD parameters of the drug and the observed concentration or effect.
References
The following sources were used to create this article:
[Rowland and Tozer's Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications]
[Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications]
[Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications]
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