COMPARTMENT MODEL

GROUP 11: Winta Triana Wahyu Alfath Firdaus Zolla Verbianti Suwita Anugrah Putra Rizki Amaliyah

COMPARTMENT MODELCompartmental models are classical pharmacokinetic models that simulate the kinetic processes of drug absorption, distribution, and elimination with little physiologic detail. (Shargel, 2004)

A compartment is a hypothetical space bound by an unspecified membrane across which drugs are transferred.The concept of compartmental analysis is used to determine what has become of the drug as a function of time from the moment it is administered until it is no longer in the body.

Most drugs administered orally can be adequately described using a one-compartment model, whereas drugs administered by rapid intravenous infusion are usually best described by a two-compartment or three-compartment model system.

ONE COMPARTMENT MODEL

The one-compartment open model offers the simplest way to describe the process of drug distribution and elimination in the body. (Shargel, 2004)

The simplest kinetic model that describes drug disposition in the body is to consider that the drug is injected all at once into a box, or compartment, and that the drug distributes instantaneously and homogenously throughout the compartment.Drug elimination also occurs from the compartment immediately after injection

Uptake of drugs by various tissue organs will occur at varying rates, depending on:the blood flow to the tissuethe lipophilicity of the drugthe molecular weight of the drug, and the binding affinity of the drug for the

tissue mass

Pharmacokinetic parameter of the one-compartment model

1. apparent volume of distribution (V D)the apparent volume of distribution is the volume in which the drug is distributed.The apparent volume of distribution assumes that the drug is uniformly distributed in the body. The V D is determined from the preinjected amount of the dose in the syringe and the plasma drug concentration resulting immediately after the dose is injected.The apparent volume of distribution is a parameter of the one-compartment model and governs the plasma concentration of the drug after a given dose.

2. elimination rate constant (k)

the elimination rate constant governs the rate at which the drug concentration in the body declines over time. The one compartment model that describes the distribution and elimination after an IV bolus dose is given in

Pharmacokinetic model for a drug administered by rapid intravenous injection. D B = drug in body; V D = apparent volume of distribution; k = elimination rate constant.

The one-compartment open model does not predict actual drug levels in the tissues. However, the model assumes that changes in the plasma levels of a drug will result in proportional changes in tissue drug levels, since their kinetic profile is consistent with inclusion within the vascular compartment and the various drug concentrations within the compartment are in equilibrium. The drug in the body, D B, cannot be measured directly; however, accessible body fluids (such as blood) can be sampled to determine drug concentrations. (Shargel, 2004)

Several assumptions are associated with modeling of drug behavior in the body. 1. It is assumed that the volume of each compartment remains constant. 2. is assumed that once a drug enters the compartment, it is instantaneously and uniformly distributed throughout the entire compartment In compartment models, 3. It is assumed that drug passes freely into and out of compartments. Thus, these compartmental systems are known as open systems. (Shargel, 2004)

In this simple one-compartment system, it is assumed that the administered drug is confined to the plasma (or blood) and then excreted.Drugs that exhibit this behavior have small volumes of distribution. For example, a drug such as warfarin sodium, which is extensively bound to plasma albumin, will have a volume of distribution equivalent to that of plasma water, about 2.8 L in an average 70-kg adult. (Ansel, 2013)

Typically, drug transport between compartments follows first-order kinetics, where in a constant fraction of drug is eliminated per unit of time and can be described by ordinary differential equations. In these linear systems, the time constants that describe the rate at which the plasma or blood concentration curve of a drug decays are independent of the dose, the volume of distribution, and the route of administration.(Ansel, 2013)

Some drugs, however, are initially distributed at somewhat different rates in various fluids and tissues.Consequently, these drugs’ kinetic behavior can best be illustrated by considering an expansion of the one-compartment system to the two-compartment model.(Ansel, 2013)

TWO COMPARTMENT MODEL

In the two-compartment system, a drug enters into and is instantaneously distributed throughout the central compartment.Its subsequent distribution into the second or peripheral compartment is slower. For simplicity, on the basis of blood perfusion and tissue–plasma partition coeffi cients for a given drug, various tissues and organs are considered together and designated either central compartment or peripheral compartment. (Ansel, 2013)

A drug that follows the pharmacokinetics of a two-compartment model does not equilibrate rapidly throughout the body, as is assumed for a one-compartment model. In this model, the drug distributes into two compartments, the central compartment and the tissue, or peripheral compartment. 1. The central compartment represents the blood, extracellular fluid, and highly perfused tissues. The drug distributes rapidly and uniformly in the central compartment. (Shargel, 2004)The central compartment is usually considered to include the blood, the extracellular space, and organs with good blood perfusion, such as lungs, liver, kidneys, and heart. (Ansel, 2013)

2. A second compartment, known as the tissue or peripheral compartment, contains tissues in which the drug equilibrates more slowly. Drug transfer between the two compartments is assumed to take place by first-order processes. (Shargel, 2004)The peripheral compartment is usually comprises tissues and organs that are poorly perfused by blood, such as skin, bone, and fat. (Ansel, 2013)

In contrast, a one-compartment model is used when the drug appears to distribute into tissues instantaneously and uniformly. For both one- and multicompartment models, the drug in the tissues that have the highest blood perfusion equilibrates rapidly with the drug in the plasma. These highly perfused tissues and blood make up the central compartment. (Shargel, 2004)

Multicompartment models were developed to explain this observation that, after a rapid IV injection, the plasma level time curve does not decline linearly as a single, first-order rate process. The plasma level time curve reflects first-order elimination of the drug from the body only after distribution equilibrium, or plasma drug equilibrium with peripheral tissues occurs. Drug kinetics after distribution is characterized by the first-order rate constant, b (or beta, ).

Relationship between tissue and plasma drug concentrations for a two-compartment open model. The maximum tissue drug concentration may be greater or less than the plasma drug concentration.

REFERENCESAnsel et all. 2013. Pharmaceutical Dosage Forms and Drug Delivery Systems. USA

Shargel et all. Applied Biopharmaceutics and Pharmacokinetics 5ed.