[Pharmacology] - Pharmacokinetics || Explaining Drug Distribution

In systemic circulation, it moves to different tissues and organs but this is affected by several factors which include;

• Bood Flow
  In the body, blood flow has different variations. Some organs get more blood, while some get little or less blood. Organs such as the Kidney, the liver, and the Brain get a lot of blood flowing into them, which would mean theoretically that drugs would get to these organs more than they would get to other organs. The organs that have less blood flowing into them include the skin and the adipose tissue. Theoretically, we could assume that these areas would get less inflow of drugs if it is basically dependent on blood flow.

• Capillary Permeability
  In cases where the tissues that carry the blood have larger gaps and pores, they can easily leak out the drug to organs that it surrounds or supplies, and drugs will be easily distributed to those organs. Capillaries such as Sinusoidal capillaries, and Fenestrated Capillaries have large pores and theoretically, drugs should be distributed more in these capillaries. Cases of Blood-Brain Barriers, or continuous capillaries where there are no intercellular clefts, and fenestration pores, reducing the ability for the movement of things out of it, except with the help of transporters, and hydrophobic drugs, it can be theoretically said that the distribution of drugs can be little compared to fenestrated and sinusoidal capillaries. You can always find these tight capillaries in the brain. In the instance when a patient has septic shock, there is an increase in capillary permeability, causing a decrease in the serum concentration of the drug in the blood but an increase in distribution.

• Protein Binding
  The liver is responsible for producing Albumin, and the kidney is responsible for not allowing the albumin to get into the urine, maintaining it in the blood rather than losing it with Urine. Albumin usually binds with a lot of drugs because so many are protein-binding drugs. In cases where there is a high plasma protein binding drug, the number of drugs concentrated in the plasma would increase while the number of free drugs available for distribution will be decreased causing the low distribution of the drugs. The albumin or protein molecules in the body serve as reservoirs for the drug releasing the drugs over time. Since albumin molecules are big and hydrophilic, they cannot get out of the bloodstream easily, so they hold on to the drugs until they release them gradually. So when there is a decrease in the distribution of the drugs, the drug distribution lasts longer. In drugs with low binding plasma protein properties, there will be excessive free drugs to be distributed, causing a decrease in plasma protein binding.

• Solubility of the Drug
  This is another important factor for drug distribution. Drug solubility explains the ability of a drug to move easily across blood vessels and membranes of cells and capillaries. Large, charged, hydrophilic drugs are very difficult to pass through the membranes of blood vessels while small, non-polar, and hydrophobic drugs can easily pass through the membranes and distribute easily. If the drug binds to Albumin, it will be very difficult to pass through the membrane because it becomes, large, and is hydrophilic (not lipid soluble).

• Volume of Distribution
  This has to do with the amount of blood with respect to the body's total fluid volume. These volumes include plasma volume, interstitial fluid volume, and intracellular fluid volume. When it occupies every type of fluid, then it has a high volume of distribution. When drugs are heavily protein bound, large, charged (polar), or hydrophilic, then they stay in the capillaries, unable to move to make them have a low volume of distribution. If a drug is a little protein bound, with lower molecular weight but still little charge, it can still move through the capillary and get to the plasma but won't go to the intracellular fluid volume, making it the medium volume of distribution. Drugs such as Warfarin are regarded as low volume of distribution drug, chloroquine is another drug regarded to have a high volume with about 150,000 liters. As a high-volume drug, it is not a plasma protein-bound drug, and they are hydrophobic.

Conclusion

Let me quickly do a recap of the entire post. The word distribution means sharing, and in pharmacokinetics, drug distribution has to do with sharing drugs from the blood to other parts of the body which includes sites of action, sites of metabolism and site of excretion, and to various tissues of the body including fat, muscles, and brain tissues. Remember that absorption is skipped for IV drugs since the drugs as directly injected into the blood vessels, so the first step of pharmacokinetics for IV drugs is distribution, distributing to interstitial or intracellular fluids. In our subsequent post, I will be taking a dive into the other aspects of Pharmacokinetics, looking at drug metabolism, drug excretion, and Drug Clearance. Thanks a lot for joining me today.

• <National Library of Medicine - Drug Distribution>

• <Intechopen.com - Drug Distribution and Drug Elimination>

• <LibreTexts libraries - Distribution>

• <Boomer.org - Factors affecting drug distribution >

• <International Society of Nephrology - Capillary leak syndrome: etiologies, pathophysiology, and management>

• <Msdmanuals.com - Drug Distribution to Tissues>

• <National Library of Medicine - Volume of Distribution>

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