In pharmacology, the volume of distribution (VD, also known as apparent volume of distribution, literally, volume of dilution [1] ) is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma. [2] In other words, it is the ratio of amount of drug in a body (dose) to concentration of the drug that is measured in blood, plasma, and un-bound in interstitial fluid. [3] [4]
The VD of a drug represents the degree to which a drug is distributed in body tissue rather than the plasma. VD is directly proportional with the amount of drug distributed into tissue; a higher VD indicates a greater amount of tissue distribution. A VD greater than the total volume of body water (approximately 42 liters in humans [5] ) is possible, and would indicate that the drug is highly distributed into tissue. In other words, the volume of distribution is smaller in the drug staying in the plasma than that of a drug that is widely distributed in tissues. [6]
In rough terms, drugs with a high lipid solubility (non-polar drugs), low rates of ionization, or low plasma protein binding capabilities have higher volumes of distribution than drugs which are more polar, more highly ionized or exhibit high plasma protein binding in the body's environment. Volume of distribution may be increased by kidney failure (due to fluid retention) and liver failure (due to altered body fluid and plasma protein binding). Conversely it may be decreased in dehydration.
The initial volume of distribution describes blood concentrations prior to attaining the apparent volume of distribution and uses the same formula.
The volume of distribution is given by the following equation:
Therefore, the dose required to give a certain plasma concentration can be determined if the VD for that drug is known. The VD is not a physiological value; it is more a reflection of how a drug will distribute throughout the body depending on several physicochemical properties, e.g. solubility, charge, size, etc.
The unit for Volume of Distribution is typically reported in litres. As body composition changes with age, VD decreases.
The VD may also be used to determine how readily a drug will displace into the body tissue compartments relative to the blood:
Where:
If you administer a dose D of a drug intravenously in one go (IV-bolus), you would naturally expect it to have an immediate blood concentration which directly corresponds to the amount of blood contained in the body . Mathematically this would be:
But this is generally not what happens. Instead you observe that the drug has distributed out into some other volume (read organs/tissue). So probably the first question you want to ask is: how much of the drug is no longer in the blood stream? The volume of distribution quantifies just that by specifying how big a volume you would need in order to observe the blood concentration actually measured.
An example for a simple case (mono-compartmental) would be to administer D=8 mg/kg to a human. A human has a blood volume of around 0.08 L/kg . [7] This gives a 100 μg/mL if the drug stays in the blood stream only, and thus its volume of distribution is the same as that is 0.08 L/kg. If the drug distributes into all body water the volume of distribution would increase to approximately 0.57 L/kg [8]
If the drug readily diffuses into the body fat the volume of distribution may increase dramatically, an example is chloroquine which has a 250-302 L/kg [9]
In the simple mono-compartmental case the volume of distribution is defined as: , where the in practice is an extrapolated concentration at time = 0 from the first early plasma concentrations after an IV-bolus administration (generally taken around 5 min - 30 min after giving the drug).
Drug | VD | Comments |
Warfarin | 8 L | Reflects a high degree of plasma protein binding. |
Theophylline, Ethanol | 30 L | Represents distribution in total body water. |
Chloroquine | 15000 L | Shows highly lipophilic molecules which sequester into total body fat. |
NXY-059 | 8 L | Highly charged hydrophilic molecule. |
Blood alcohol content (BAC), also called blood alcohol concentration or blood alcohol level, is a measurement of alcohol intoxication used for legal or medical purposes.
In physiology, body water is the water content of an animal body contained in its tissues, blood, bones, and elsewhere. The percentages of body water contained in various fluid compartments add up to total body water (TBW). This water makes up a significant fraction of the human body, both by weight and by volume. Ensuring the right amount of body water is part of fluid balance, an aspect of homeostasis.
Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs. The effects can include those manifested within animals, microorganisms, or combinations of organisms.
Physiologically based pharmacokinetic (PBPK) modeling is a mathematical modeling technique for predicting the absorption, distribution, metabolism and excretion (ADME) of synthetic or natural chemical substances in humans and other animal species. PBPK modeling is used in pharmaceutical research and drug development, and in health risk assessment for cosmetics or general chemicals.
In pharmacology, clearance is a pharmacokinetic parameter representing the efficiency of drug elimination. This is the rate of elimination of a substance divided by its concentration. The parameter also indicates the theoretical volume of plasma from which a substance would be completely removed per unit time. Usually, clearance is measured in L/h or mL/min. The quantity reflects the rate of drug elimination divided by plasma concentration. Excretion, on the other hand, is a measurement of the amount of a substance removed from the body per unit time. While clearance and excretion of a substance are related, they are not the same thing. The concept of clearance was described by Thomas Addis, a graduate of the University of Edinburgh Medical School.
Biological half-life is the time taken for concentration of a biological substance to decrease from its maximum concentration (Cmax) to half of Cmax in the blood plasma. It is denoted by the abbreviation .
Distribution in pharmacology is a branch of pharmacokinetics which describes the reversible transfer of a drug from one location to another within the body.
The initial volume of distribution (Vi) is a pharmacological term used to quantify the distribution of a drug throughout the body relatively soon after oral or intravenous dosing of a drug and prior to the drug reaching a steady state equilibrium. Following distribution of the drug, measurement of blood levels indicate the apparent volume of distribution. Calculation of the initial volume of distribution is the same calculation as that for the apparent volume of distribution, given by the equation:
Context-sensitive half-life or context sensitive half-time is defined as the time taken for blood plasma concentration of a drug to decline by one half after an infusion designed to maintain a steady state has been stopped. The "context" is the duration of infusion.
Plasma protein binding refers to the degree to which medications attach to blood proteins within the blood plasma. A drug's efficacy may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse or diffuse through cell membranes. Common blood proteins that drugs bind to are human serum albumin, lipoprotein, glycoprotein, and α, β‚ and γ globulins.
Acecainide is an antiarrhythmic drug. Chemically, it is the N-acetylated metabolite of procainamide. It is a Class III antiarrhythmic agent, whereas procainamide is a Class Ia antiarrhythmic drug. It is only partially as active as procainamide; when checking levels, both must be included in the final calculation.
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific substance after administration. The substances of interest include any chemical xenobiotic such as pharmaceutical drugs, pesticides, food additives, cosmetics, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics is based on mathematical modeling that places great emphasis on the relationship between drug plasma concentration and the time elapsed since the drug's administration. Pharmacokinetics is the study of how an organism affects the drug, whereas pharmacodynamics (PD) is the study of how the drug affects the organism. Both together influence dosing, benefit, and adverse effects, as seen in PK/PD models.
In pharmacokinetics, a compartment is a defined volume of body fluids, typically of the human body, but also those of other animals with multiple organ systems. The meaning in this area of study is different from the concept of anatomic compartments, which are bounded by fasciae, the sheath of fibrous tissue that enclose mammalian organs. Instead, the concept focuses on broad types of fluidic systems. This analysis is used in attempts to mathematically describe distribution of small molecules throughout organisms with multiple compartments. Various multi-compartment models can be used in the areas of pharmacokinetics and pharmacology, in the support of efforts in drug discovery, and in environmental science.
The elimination rate constantK or Ke is a value used in pharmacokinetics to describe the rate at which a drug is removed from the human system.
Cmin is a term used in pharmacokinetics for the minimum blood plasma concentration reached by a drug during a dosing interval, which is the time interval between administration of two doses. This definition is slightly different from Ctrough, the concentration immediately prior to administration of the next dose. Cmin is the opposite of Cmax, the maximum concentration that the drug reaches. Cmin must be above certain thresholds, such as the minimum inhibitory concentration (MIC), to achieve a therapeutic effect.
In the field of pharmacokinetics, the area under the curve (AUC) is the definite integral of the concentration of a drug in blood plasma as a function of time. In practice, the drug concentration is measured at certain discrete points in time and the trapezoidal rule is used to estimate AUC. In pharmacology, the area under the plot of plasma concentration of a drug versus time after dosage gives insight into the extent of exposure to a drug and its clearance rate from the body.
The plateau principle is a mathematical model or scientific law originally developed to explain the time course of drug action (pharmacokinetics). The principle has wide applicability in pharmacology, physiology, nutrition, biochemistry, and system dynamics. It applies whenever a drug or nutrient is infused or ingested at a relatively constant rate and when a constant fraction is eliminated during each time interval. Under these conditions, any change in the rate of infusion leads to an exponential increase or decrease until a new level is achieved. This behavior is also called an approach to steady state because rather than causing an indefinite increase or decrease, a natural balance is achieved when the rate of infusion or production is balanced by the rate of loss.
In pharmacology, the elimination or excretion of a drug is understood to be any one of a number of processes by which a drug is eliminated from an organism either in an unaltered form or modified as a metabolite. The kidney is the main excretory organ although others exist such as the liver, the skin, the lungs or glandular structures, such as the salivary glands and the lacrimal glands. These organs or structures use specific routes to expel a drug from the body, these are termed elimination pathways:
Custirsen, with aliases including custirsen sodium, OGX-011, and CC-8490, is an investigational drug that is under clinical testing for the treatment of cancer. It is an antisense oligonucleotide (ASO) targeting clusterin expression. In metastatic prostate cancer, custirsen showed no benefit in improving overall survival.
Balanced anesthesia is an anesthetic method for surgical patients during their operation. The method was proposed by John Lundy in 1926. The purpose of balanced anesthesia is to use multiple anesthetic agents for a safer general anesthesia and to mitigate the potential adverse side effects which may be caused by the anesthetic agents. The concept of balanced anesthesia is that of applying two or more medications or techniques in order to ease pain, relax the muscles, and have autonomous reflexes suppressed in the patient. In other words, it is an anesthesia method to maintain stable vital signs. There are numerous factors that come into play when the anesthetist decides to use this method of anesthesia. These factors include, but are not limited to: patients' major organ functions, general condition and compensatory capacity. By making use of adequate types and appropriate amounts of agents and accurate anesthesia methods, the anesthetist will promote a successful, safe, and efficient surgery.