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. compartment is included. Tissue compartments may include both normal and deep distribution (adapted from Vallabhaneni, 2014). Multi-Compartment Model
Drug permeation takes the form of four main mechanisms: 1. Aqueous diffusion.
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 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 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 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 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 Drug distribution Distribution involves movement of the drug from the administration site to the area targeted for a specific desired effect of the drug. Distribution of drug molecules depends on many interrelated factors, including blood flow, binding of the drug and barriers between body compartments. Some drug molecules are deposited in storage areas along the route, and some are rendered inactive or never distributed. Tissue with the most abundant blood flow tends to receive the drug first; increased blood flow to the tissue means increased
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 to cross water barriers between cells. Some substances may increase or decrease the drug’s absorption. Grapefruit juice, for example, enhances drug absorption. Drugs are typically absorbed less efficiently through skin or mucous membranes than oral or parenteral routes. The rate of rectal and sublingual absorption is relatively rapid due to the abundant blood supply available to the mucosal surfaces. Liquid medicines are absorbed more quickly than solid preparations. Lipid-soluble drugs are absorbed quickly, while enteric coatings slow absorption. Injected drugs will absorb at varying degrees according to tissue perfusion of the site. Intradermal drugs travel from the injection site into the capillaries more slowly than subcutaneously administered drugs. Drugs injected into the muscle will absorb even more quickly due to the abundant supply of blood to the muscles. Fat acts as a storage location for lipid-soluble drugs (like anticoagulants). Drugs may accumulate there, building up and remaining for an extended period, and releasing long after administration of the drug is complete. uptake of a drug. Tissues receiving the most blood, like the brain and kidney, have the highest rate of uptake, while tissues with low blood supply, like fat, accumulate the drug at a slower rate. Highly vascular organs like the liver, kidney and heart will acquire the drug more quickly than bone, muscle, fat or skin tissues, which have low vascularity. Other characteristics of the individual, including activity level and tissue temperature, can also affect the drug’s distribution to the skin and muscle.
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Book Code: MTX1324B
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