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| Pharmacokinetic Modeling Physiologically-based pharmacokinetic modeling (PBPK) is a mathematical modeling technique for prediction of the absorption, distribution, metabolism and excretion (ADME) of a compound in humans and other species used in pharmaceutical research. Pharmacokinetic models are relatively simple mathematical schemes that represent complex physiologic spaces or processes. Accurate PK modeling is important for precise determination of absorption and elimination rates, area under the curve (AUC), time to reach the maximum concentration (tmax), and half life (t1/2). The most commonly used pharmacokinetic models are 1-compartment and 2-compartment. In the one compartment model, the product initially distributes into a central compartment (Vc) before distributing into the peripheral compartment (Vt). If a drug, for example, rapidly equilibrates with the tissue compartment, then, for practical purposes, we can use the much simpler one-compartment first-order model which uses only one volume term, the apparent volume of distribution, Vd. A log scale plot of the serum level decay curve of a 1-compartment model yields a straight line. Drugs which exhibit a slow equilibration with peripheral tissues are best described with a two compartment first-order model. A log scale plot of the serum level decay curve of a 2-compartment model yields a biphasic line. Note that during the initial, rapidly declining distribution phase, drug is moving from the central compartment to the tissue compartment. Failure to consider the distribution phase can lead to significant errors in estimates of elimination rate and in prediction of the appropriate dosage. Unless you are using a two-compartment model, you should not use a level drawn during the distribution phase to calculate the elimination rate. Elimination of drug is the predominant process during the second phase of the biphasic plot. Because elimination is a first-order process, the log plot of this phase is a straight line. Walker Downey & Associates, Inc. uses its expert Statistical Services to help clients evaluate their PBPK data. Case Studies
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