Definition of the main pharmacokinetic parameters

Pharmacokinetics is based on the study of the variation of plasma concentrations of drugs, because it is the only easily accessible parameter. Before approaching it, it is necessary to know the definitions of the terms usually used:

  1. The plasma half-life of a drug (T ½) is the time necessary to halve the plasma concentration, for example to decrease from 100 to 50 mg/L. The knowledge of the half-life is useful for the determination of the frequency of administration of a drug (the number of intakes per day) for obtaining the desired plasma concentration. Generally, the half-life of a particular drug is independent of the dose  administered. In certain exceptional cases, it varies with the dose: it can increase or decrease according to, for example, the saturation of a mechanism (elimination, catabolism, binding to plasma proteins etc).
  2. The area under curve, AUC, corresponds to the integral of the plasma concentration versus an interval of definite time. In practice, the approximation is used:
    AUC = ƒ ([C] x Dt)
    [C]: is measured concentration and Dt: interval of time between two measurements. The precision of the AUC grows with the number of measurements of concentration taken. The AUC is expressed in mass (mg, g) X liter-1 X hour. One of its interests is to allow the measurement of the bioavailability of a drug.
  3. The bioavailability indicates the percentage of the administered drug which arrives in the central compartment. It is generally measured by comparing the AUC obtained after intravenous administration and after oral administration, for example. After intravenous administration, the AUC obtained corresponds to a bioavailability which, by definition, is 100%; after oral administration, the AUC corresponds at best to an identical bioavailability. It is generally lower, sometimes null.
  4. The compartment indicates the fictitious volume in which a drug would be distributed. It can correspond or not to a real volume, for example the volume of blood called first compartment, or the whole body except blood, called second compartment. The real anatomical sectors in which the drug is distributed at different concentrations is represented by one, two, rarely three virtual compartments where the concentration of the drug is regarded as homogeneous. The concept of compartment thus makes it possible to model the fate of a drug .
  5. The volume of distribution (Vd) is the fictitious volume, expressed in liter or in liter per kilogram, in which the drug would have been distributed by supposing that its concentration is homogeneous, i.e. the average tissue concentration is identical to that of the plasma.  It is expressed as Vd = dose/C0 (initial concentration). For example, after intravenous injection of 100 mg of a drug whose initial concentration, C0, in plasma is 10 mg/L, the volume of distribution is of 10 L . For a given drug, the knowledge of its desirable concentration in blood and of its volume of distribution allows evaluation of the dose to administer.
  6. Clearance is the fraction of a theoretical volume completely purified (i.e. no longer containing any of the drug concerned) per unit of time. Plasma clearance is the apparent volume of plasma purified per unit of time. Total clearance (Clt) is the fraction of the volume of distribution, Vd, which is completely purified per unit of time. The total clearance depends on the constant of elimination and thus on T ½ and on Vd. Clearance is a constant in linear kinetics.
  7. Steady state concentration, Css, corresponds to the state of equilibrium obtained at the end of a certain number of administrations. To obtain an increase in the plasma concentration with repeated administrations, it is necessary that a residual concentration persists at the time of the following administration. At the steady state, if the dose and the frequency of administrations remain constant, the concentration obtained will also be constant. The steady state is obtained at the end of approximately five half-lives.

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Quizz : Q 163
In pharmacokinetics, compartment:
indicates necessarily the extracellular volume in which the drug is distributed
indicates a real or fictitious volume in which the drug is distributed
indicates body surface area
is a concept allowing better simulation of the fate of a drug
indicates necessarily the blood volume

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