Distribution: The Second Stage of Pharmacokinetics

Updated: 5 days ago

Distribution is the second stage of pharmacokinetics and is the process of how medications are dispersed throughout the body through the bloodstream. This process is reversible, so certain molecules may connect with receptors inside cells or atop cell membranes, and other molecules might flow back into the bloodstream.


The transportation of a drug from the bloodstream to the drug target site depends on the blood flow, capillary permeability (the ability of capillary walls that permits the trade of certain fat-soluble molecules), plasma protein binding, the blood-brain barrier, and the placental barrier, alongside the corresponding lipid-solubility of the drug molecule. Moreso, other aspects involve the ability of the drug’s attachment to blood and tissue proteins and volume distribution.


There is a difference in blood flow to various organs of the body. The most important organs of the body get the greatest supply of blood, like the brain, liver, and kidneys. Fat tissues get the least amount of blood while skeletal and bone gain less blood. In a process called redistribution, drugs are distributed to organs and tissues with greater blood flow and then go to tissues and organs with lesser blood flow. Over time following drug administration, drug concentration in the blood, tissues, and organs achieve an equilibrium.


Fewer drugs can enter the central nervous system due to the blood-brain barrier, an anatomical barrier that halts substances getting to the brain due to the capillary impermeability in the brain. For entrance into the brain, drugs need to be small and lipid-soluble or trafficked by the carrier-mediated transport mechanisms in the central nervous system.


Medication distribution may result in unintentional adverse side effects. Drugs are created to result in one effect, so they bind strongly to one receptor site and reliably result, or halt, an action. Despite this, adverse side effects can happen when the drug binds to additional sites alongside the target site, resulting in secondary adverse side effects.

The Four Stages of Pharmacokinetics


Blood Flow

The blood flow, or circulatory system, traffics drugs to their target site of the body. Various aspects can influence the blood flow and transportation of drugs, like weakened pumping by the heart muscle, blocked vessels, constricted vessels, and decreased flow.


When the drug enters the bloodstream, a part of it will exist as a free drug, dissolved in plasma. A portion of the drug will be reversibly taken by red cells, while some will be reversibly bound to plasma proteins. Most of the bound forms of the drug-span cell membranes yield the desired effect. These protein-bound drugs can serve as a reserve that dispenses the drug slowly and extends its influence.

Factors Influencing Drug Distribution


Protein-Binding

Certain drugs will stay in the blood, incapable to circulate out of the bloodstream to the target site. Due to the plasma in blood having various proteins, some of them reversibly bind to drugs in a method called plasma protein binding.


Drug-binding plasma proteins absorb the drug binding to it. Once attached to the protein, the drug will stay in the bloodstream and be incapable of getting to the target site. Activation of the receptors necessitates a great amount of the drug to absorb the protein binding sites in the blood. The extent of the drug hinges on the efficacy of the drug binding to the proteins.

Competition of other drugs for the binding sites complicates protein binding.


When a different drug is added, that binds to the same site, it will expel part of the original drug, expanding the number that gets to the target site. The significance of the exchange hinges on the drug's efficacy to bind to the plasma proteins.

Demonstration of Plasma Protein Binding


Blood-Brain Barrier

The blood-brain barrier is an additional layer that divides the bloodstream from the brain. It is made by tight junctions of endothelial cells, the cells that line blood vessels. The tight junctions in the blood-brain barrier restrict certain substances from entering through capillaries.


The blood-brain barrier keeps a stable environment for the brain and defends it from various substances or neurotransmitters from different areas of the body. Due to this, certain drugs cannot traverse the barrier.

Comparable barriers are present in other areas of the body. The placental barrier exists between a fetus and others; however, the barrier is more permeable to drugs and various substances. The cerebrospinal fluid is defended by a barrier that allows certain substances that are stopped by the blood-brain barrier.


Illustration of the Blood-Brain Barrier


Outlook

Distribution in pharmacokinetics is the mechanism of a drug spreading in the body through the bloodstream.


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Laxxon Medical is dedicated to engineering patented 3D pharmaceutical solutions which optimize products and benefit patients. Our goal is to establish SPID®-Technology as a manufacturing process that has the individual and the pharmaceutical partner in mind.



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