Lh x C CLhu x Cu[25

in which CLH u is the clearance based on unbound concentration. When CLint is low, CLint e CLH u.

Changes infu (e.g., due to saturation or displacement) and/or in CLHu (e.g., by enzymatic inhibition or induction) will induce changes in CLH.

Protein binding is one of the factors that influences CLR. Filtration and secretion depend onfu and change in the same way.15

At steady-state, increase offu will decrease C, but Cu will be the same, as CLu should not be affected and the activity of the drug should not change, despite the decrease of C.

The distribution volume VD represents the theoretical body volume inside which the drug would be distributed if it had the same concentration everywhere in the body and in plasma. VD equals the amount of drug in the body divided by the plasma concentration:

This definition is simple to use but not sufficient. Indeed, according to this equation VD increases between the moment the drug reaches the body and the moment its distribution is complete. A condition must be added, that the drug be in equilibrium in all parts of the distribution volume, a variation in one part being immediately reflected in all other parts. This condition is fulfilled during the elimination phase when plasma and tissue concentrations decrease in parallel, which means that the ratio of tissue concentration over plasma concentration is constant.

With this condition, the amount of drug remaining in the body (Mt) at time t after an intravascular administration is equal to the initial dose minus the amount eliminated:

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