Biophase equilibration

P. Veng-Pedersen, J. W. Mandema, and M. Danhof, Biophase equilibration times. J Pharm Sci 80 881-886 (1991). 

LSA AND Biophase Distribution Kinetics — Biophase Equilibration Times... 

The //-type biophase equilibration time, BET, is defined as the time it takes to reach p percent of SS in the biophase when the drug is infused IV at a constant rate, R. For a drug with a linear disposition, this parameter depends on both the unit impulse response and the conduction function and can be obtained numerically from the following relationship ... 

The equilibration of drug between plasma and biophase is determined by the parameter KeQ and the equilibration half-time In 21 Keg, and T ITEe is the length of time it takes for plasma concentration and effective concentration to reach equilibrium this time can range from a few minutes to several hours. For drugs with short half-time, the value of KCq is large and an equilibration is reached fast, and thus the plasma concentration is a good indicator of biophase levels for drugs with low Kcg (lower than the terminal elimination-rate constant), an equilibrium will never be reached. The time at which peak concentration is achieved (Te ) is expressed as... 

Although the pharmacodynamic effect is primarily a function of the concentration of a drug at the site of action and the affinity of the drug for the receptors, time-dependent processes such as ADME also influence the observed effect. Consequently, the pharmacodynamic effect is also a function of time, especially under in vivo conditions where drug molecules may not equilibrate rapidly with the biophase. Recently, relationships between plasma concentrations of drugs and pharmacodynamic effects have received considerable attention. The mathematical analysis of the relationships between pharmacokinetics and pharmacodynamics is often termed... 

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