Measurements of drug concentrations may be taken by invasive methods (blood or spinal fluid, for example) or non-invasive methods, as in the case of urine, feces or saliva samples. The concentration of the drug in plasma (the liquid portion of blood) serves as a reference point for the amount of drug in the body’s compartments because the drug is fairly evenly distributed and can be sampled fairly easily. Plasma is in constant contact with body tissues as it distributes the blood to body compartments. Plasma concentration is measured by taking a sample of blood. from passing through special barriers, called lipid barriers , which separate aqueous compartments of the body. Where the lipid partitions and aqueous compartments border one another, the drug molecule will move from one compartment to another in a predictable way, depending on properties of the chemical and each compartment. Special carrier molecules are able to carry substances necessary for cell function but too large or insoluble to pass through lipid barriers. Very large substances that are unable to pass though barriers, even with the help of special carriers, may use endocytosis, a process in which the substance is engulfed by the cell membrane, where it is broken down and released. The reverse of this process, exocytosis, causes the secretion of a substance from a cell. Tissue compartments may include both normal and deep distribution (adapted from Vallabhaneni, 2014). Multi-Compartment Model Administered Dosage Release Dosing Compartment Absorption Central Compartment Normal Distribution Tissue Compartment Deep Elimination may occur from each compartment words, bioavailability is the fraction (or percentage) of the administered dose that reaches systemic circulation. Changes in the drug’s absorption rate and degree of bioavailability affect the duration of drug action and drug effectiveness. Different drug routes vary in their efficiency or complete use of the drug. Administered drugs may have less than 100 percent of the drug available due to incomplete absorption and first-pass elimination, which is discussed below. Medications taken by mouth may not be completely absorbed. Their low bioavailability is due to the fact that the drug may be too hydrophilic or lipophilic to be completely absorbed; drugs that are too hydrophilic cannot cross lipid membranes, while lipophilic drugs are not soluble enough
The administration route is chosen for its convenience as well as the associated bioavailability. Hepatic first-pass effect can be avoided by using inhaled drugs, under-the- tongue tablets or transdermal administration, all of which bring the drug into systemic circulation through a vascular network. Drugs administered through rectal suppositories avoid hepatic first-pass effect to a lesser degree than either transdermal or sublingual administration, with about half of the drugs absorbed through vessels that empty into the inferior vena cava; the other half of the rectal dose moves into an area where veins feed into the liver. administration site and distributed to its target action site. To do this, the drug must permeate through the barriers that separate the compartments of the body. These barriers include the tissues that make up the intestinal walls, capillaries that line the gut, and the blood-brain barrier – the walls of the capillaries bordering the brain. Drug permeation takes the form of four main mechanisms: 1. Aqueous diffusion. Principles of permeation A drug must be absorbed into the blood from its
2. Lipid diffusion. 3. Special carriers. 4. Endocytosis and exocytosis.
Aqueous diffusion occurs within compartments of the body (called aqueous compartments ) and across certain membranes with porous linings. Most drugs are prohibited
Compartments of the body Compartment models treat the body as a set of
interconnected compartments: Within each compartment, the drug concentration (percentage of drug) is assumed to be evenly (homogenously) distributed, and movement of the drug between the compartments proceeds in a predictable way. Most drugs exhibit properties of multicompartment pharmacokinetics, meaning the drug accumulates and is eliminated from different compartments of the body at varying rates, resulting in different concentrations of the drug in different compartments of the body. The number of compartments in the simplest models typically includes a compartment associated with the administration route. If the release from dosage form is very fast, as is the case in IV injection or with use of a dissolved drug, no dosing compartment is included. Tissue compartments may include both normal and deep distribution (adapted from Vallabhaneni, 2014). The number of compartments in the simplest models typically includes a compartment associated with the administration route. If the release from dosage form is very fast, as is the case in IV injection or with use of a dissolved drug, no dosing compartment is included. Absorption To be of any use to the body, drugs must be absorbed. Absorption moves the drug from the area of administration into the circulatory or lymphatic systems. The term “bioavailability” refers to the percentage or proportion of the administered drug that has entered the circulatory system and is available to produce the effect. Intravenously administered drugs are typically 100 percent bioavailable because they are administered directly into circulation, with potentially all of the drug causing an effect. When drugs are administered by other means, topically or orally, for example, a portion of the drug’s molecules are lost in the process and will not be absorbed and distributed, reducing bioavailability of the drug. In other
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