The one-compartment open model assumes the body acts as a single, uniform compartment where a drug distributes and eliminates immediately after intravenous injection. The model is described by two parameters: the apparent volume of distribution (VD), which governs drug concentration, and the elimination rate constant, which governs the rate of decline. Clearance represents drug elimination from the body as a volume cleared per unit time and remains constant, unlike elimination expressed as an amount. The one-compartment model provides a simple description of drug distribution and elimination but does not reflect actual tissue drug levels.
The one-compartment open model assumes the body acts as a single, uniform compartment where a drug distributes and eliminates immediately after intravenous injection. The model is described by two parameters: the apparent volume of distribution (VD), which governs drug concentration, and the elimination rate constant, which governs the rate of decline. Clearance represents drug elimination from the body as a volume cleared per unit time and remains constant, unlike elimination expressed as an amount. The one-compartment model provides a simple description of drug distribution and elimination but does not reflect actual tissue drug levels.
The one-compartment open model assumes the body acts as a single, uniform compartment where a drug distributes and eliminates immediately after intravenous injection. The model is described by two parameters: the apparent volume of distribution (VD), which governs drug concentration, and the elimination rate constant, which governs the rate of decline. Clearance represents drug elimination from the body as a volume cleared per unit time and remains constant, unlike elimination expressed as an amount. The one-compartment model provides a simple description of drug distribution and elimination but does not reflect actual tissue drug levels.
The one-compartment open model assumes the body acts as a single, uniform compartment where a drug distributes and eliminates immediately after intravenous injection. The model is described by two parameters: the apparent volume of distribution (VD), which governs drug concentration, and the elimination rate constant, which governs the rate of decline. Clearance represents drug elimination from the body as a volume cleared per unit time and remains constant, unlike elimination expressed as an amount. The one-compartment model provides a simple description of drug distribution and elimination but does not reflect actual tissue drug levels.
Uttom Kumar B Pharm & M Pharm (DU), PhD (ICL, UK) Assist Professor Dept of Pharmaceutical Technology University of Dhaka 2 ASSUMPTIONS The one-compartment open model offers the simplest way to describe the process of drug distribution and elimination in the body. This model assumes that – Drug can enter or leave the body (i.e., the model is "open") Body acts like a single, uniform compartment The simplest route of drug administration from a modelling perspective is a rapid intravenous injection (IV bolus) 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 3
Parameters of the one-compartment model
Apparent volume of distribution - Governs the plasma concentration of the drug after a given dose Elimination rate constant - Governs the rate at which the drug concentration in the body declines over time
Limitations of the one-compartment model
One-compartment open model does not predict actual drug levels in the tissues Drug in the body cannot be measured directly 4 ELIMINATION RATE CONSTANT The rate of elimination for most drugs from a tissue or from the body is a first-order process, in which the rate of elimination is dependent on the amount or concentration of drug present. Total removal or elimination of the parent drug from this compartment is effected by metabolism (biotransformation) and excretion. The elimination rate constant represents the sum of each of these processes: 5 APPARENT VOLUME OF DISTRIBUTION (VD) The volume of distribution represents a volume that must be considered in estimating the amount of drug in the body from the concentration of drug found in the sampling compartment. The volume of distribution is also the apparent volume (V D) in which the drug is dissolved. Because the value of the volume of distribution does not have a true physiologic meaning in terms of an anatomic space, the term apparent volume of distribution is used. The VD relates the concentration of drug in plasma (Cp) and the amount of drug in the body (DB), as in the following equation: 6 CALCULATION OF VD
In a one-compartment model (IV administration), the VD is calculated with
the following equation: 7 SIGNIFICANCE OF VD The apparent volume of distribution is not a true physiologic volume. Most drugs have an apparent volume of distribution smaller than, or equal to, the body mass. For some drugs, the volume of distribution may be several times the body mass.
Drugs with a large apparent VD are more concentrated in extravascular
tissues and less concentrated intravascularly. If a drug is highly bound to plasma proteins or remains in the vascular region, then Cp0 will be higher, resulting in a smaller apparent VD. Consequently, binding of a drug to peripheral tissues or to plasma proteins will significantly affect VD. Thus, the apparent VD is a useful parameter in considering the relative amounts of drug in the vascular and in the extravascular tissues. 8 SIGNIFICANCE OF VD For each drug, the apparent VD is a constant. In certain pathologic cases, the apparent VD for the drug may be altered if the distribution of the drug is changed. For example, in oedematous conditions, the total body water and total extracellular water increase; this is reflected in a larger apparent VD value for a drug that is highly water soluble. Similarly, changes in total body weight and lean body mass (which normally occur with age) may also affect the apparent VD.
Lean Body Weight = 50 kg + 2.3 Kg per inch over 5 ft (Male)
= 45.5 kg + 2.3 Kg per inch over 5 ft (Female)
9 CLEARANCE Clearance is a measure of drug elimination from the body without identifying the mechanism or process. Clearance (drug clearance, systemic clearance, total body clearance, ClT) considers the entire body as a drug-eliminating system from which many elimination processes may occur.
Drug Clearance in the One-Compartment Model
Drug clearance refers to the volume of plasma fluid that is cleared of drug per unit time. Clearance may also be considered as the fraction of drug removed per unit time multiplied by the V D. The rate of drug elimination may be expressed in several ways – a. Drug Elimination Expressed as Amount Per Time Unit b. Drug Elimination Expressed as Volume Per Time Unit c. Drug Elimination Expressed as Fraction Eliminated Per Time Unit 10 Drug Elimination Expressed as Amount Per Time Unit The expression of drug elimination from the body in terms of mass per unit time (eg, mg/min, or mg/hr) is simple, absolute, and unambiguous. For a zero-order elimination process, expressing the rate of drug elimination as mass per unit time is convenient because the rate is constant. In contrast, the rate of drug elimination for a first-order elimination process is not constant and changes with respect to the drug concentration in the body. 11 Drug Elimination Expressed as Volume Per Time Unit Clearance is a concept that expresses "the rate of drug removal" in terms of volume of drug solution removed per unit time (at whatever drug concentration in the body prevailing at that time) Clearance (volume of fluid removed of drug) for a first-order process is constant regardless of the drug concentration because clearance is expressed in volume per unit time rather than drug amount per unit time. Mathematically, the rate of drug elimination is similar to Equation- 12 Drug Elimination Expressed as Fraction Eliminated Per Time Unit Consider a compartment volume, containing VD liters. If Cl is expressed in liters per minute (L/min), then the fraction of drug cleared per minute in the body is equal to Cl/VD.
Expressing drug elimination as the fraction of total drug eliminated is
applicable regardless or whether one is dealing with an amount or a volume. This approach is most flexible and convenient because of its dimensionless nature.
