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The most common and the most desirable route of drug administration is the oral route in which dosage forms (drug products) such as tablets, capsules, or oral solutions are generally used. In order to develop pharmacokinetic models to describe and predict drug disposition kinetically, the model must account for both the route of administration and the pharmacokinetic behavior of the drug in the body. Once drug disposition can be predicted by a pharmacokinetic model, then dosing regimens for individuals or groups of patients can be calculated.

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The one-compartment open model is the simplest way to describe the process of drug distribution and elimination in the body. This model assumes that the drug can enter or leave the body (ie, the model is “open”), and the entire body acts like a single, uniform compartment. The simplest route of drug administration from a modeling perspective is a rapid intravenous injection (IV bolus). The simplest pharmacokinetic model that describes drug disposition in the body is the IV bolus model where the drug is injected all at once into a box (the human body) or compartment, and the drug distributes/equilibrates instantaneously and rapidly throughout the compartment. Drug elimination from the compartment also begins to occur immediately after the IV bolus injection.

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Of course, this model is a simplistic view of drug disposition in the body, which in reality is infinitely more complex than a single compartment. In the body, when a drug is given in the form of an IV bolus, the entire dose of drug enters the bloodstream immediately, and the drug “absorption process” into the plasma is considered to be instantaneous. In most cases, the drug quickly distributes via the circulatory system to potentially all the tissues in the body. Uptake of drugs by various tissue organs will occur at varying rates and extents, depending on the blood flow to the tissue, the lipophilicity of the drug, the molecular weight of the drug, and the binding affinity of the drug for the tissue mass. Most drugs are eliminated from the body either through the kidney and/or by being metabolized in the liver. Because of rapid drug equilibration between the blood and tissues, drug distribution and elimination occur as if the dose is all dissolved in a tank of uniform fluid (a single compartment) from which the drug is eliminated. The volume in which the drug seems to be distributed is termed the apparent volume of distribution, VD. The apparent volume of distribution assumes that the drug is theoretically rapidly and uniformly distributed in the body throughout the apparent volume. The VD is determined from the injected amount or the dose and the plasma drug concentration Cp0 immediately after injection. For simplicity, it is assumed that the injected dose disperses and distributes instantly. This model is also termed a well-stirred one-compartment model. If the plasma drug concentration–time curve is not linear on a semilog plot after an ...

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