Residue Concentrations in Relation to Administered Dose

Residue concentrations and their depletion profiles are inevitably linked to administered dose of an antimicrobial drug, albeit in a possibly complex and tissue dependent manner. This is illustrated first by the equation linking, for a systemically administered drug, dose to area under the plasma/blood concentration-time curve  

In relation to drug residues, a pharmacokinetic property of major significance is the very late terminal elimination half-life (see Sections 2.3.1 and 2.7.1). For many drug classes, a semi-logarithmic plot of plasma concentration versus time, after intravenous dosing, reveals a 

There are two equations which can be used to represent terminal half-life  

This equation is the mathematical expression of the definition of a half-life, specifically, the time required for plasma concentrations to be divided by 2 after reaching pseudoequilibrium as X3 is a hybrid parameter related to Varea (the volume of distribution associated with the terminal phase) and plasma clearance. Equation (2.3) can be re-written in a more mechanistically useful way as follows  

Equation (2.3) is conceptually useful in indicating that, when slope (X3) is shallow, half-life will be long and therefore WhT will also be long. Equation (2.4) is mechanistically useful in illustrating that T j2 depends on Cl, rate of elimination from the body, and Faiea, on the extent of distribution within the body. Clearly, if Cl is slow, Tij2 will be prolonged. 

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