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There are various competing calculation methods for the drug accumulation ratio, yielding somewhat different results. A commonly used formula defines R ac as the ratio of the area under the curve (AUC) during a single dosing interval under steady state conditions to the AUC during a dosing interval after one single dose: [ 1 ]
Pharmacokinetics (from Ancient Greek pharmakon "drug" and kinetikos "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific substance after administration. [1]
The use of trapezoidal rule in AUC calculation was known in literature by no later than 1975, in J.G. Wagner's Fundamentals of Clinical Pharmacokinetics. A 1977 article compares the "classical" trapezoidal method to a number of methods that take into account the typical shape of the concentration plot, caused by first-order kinetics. [8]
The first pharmacokinetic model described in the scientific literature [2] was in fact a PBPK model. It led, however, to computations intractable at that time. The focus shifted then to simpler models, [3] for which analytical solutions could be obtained (such solutions were sums of exponential terms, which led to further simplifications.)
PK/PD relationships can be described by simple equations such as linear model, Emax model or sigmoid Emax model. [5] However, if a delay is observed between the drug administration and the drug effect, a temporal dissociation needs to be taken into account and more complex models exist: [6] [7] Direct vs Indirect link PK/PD models
The plateau principle is a mathematical model or scientific law originally developed to explain the time course of drug action (pharmacokinetics). [1] The principle has wide applicability in pharmacology, physiology, nutrition, biochemistry, and system dynamics.
Peak-to-trough ratio in pharmacokinetics is the ratio of peak (C max) and trough (C min) levels of a drug over its dosing interval (τ) at steady state.. Peak-to-trough ratio (PTR), also known as peak-to-trough variation or peak-to-trough fluctuation, is a parameter in pharmacokinetics which is defined as the ratio of C max (peak) concentration and C min (trough) concentration over a dosing ...
So, for example, digoxin has a half-life (or t 1 / 2 ) of 24–36 h; this means that a change in the dose will take the best part of a week to take full effect. For this reason, drugs with a long half-life (e.g., amiodarone , elimination t 1 / 2 of about 58 days) are usually started with a loading dose to achieve their desired ...