Absorption (pharmacology)

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Absorption (pharmacokinetics)
)

Absorption is the journey of a drug travelling from the site of administration to the site of action.[1][2]

The drug travels by some

Intravascular administration does not involve absorption, and there is no loss of drug.[4] The fastest route of absorption is inhalation.[5]

Absorption is a primary focus in drug development and medicinal chemistry, since a drug must be absorbed before any medicinal effects can take place. Moreover, the drug's pharmacokinetic profile can be easily and significantly changed by adjusting factors that affect absorption.

Dissolution

Oral ingestion is the most common route of administration of pharmaceuticals.

kidneys.[7]

The rate of dissolution is a key target for controlling the duration of a drug's effect, and as such, several dosage forms that contain the same active ingredient may be available, differing only in the rate of dissolution. If a drug is supplied in a form that is not readily dissolved, it may be released gradually and act for longer. Having a longer duration of action may improve

compliance since the medication will not have to be taken as often. Additionally, slow-release dosage forms may maintain concentrations within an acceptable therapeutic range over a longer period, whereas quick-release dosage forms may have sharper peaks and troughs in serum concentration.[8]

The rate of dissolution is described by the

Noyes–Whitney equation
as shown below:

Where:

As can be inferred from the Noyes–Whitney equation, the rate of dissolution may be modified primarily by altering the surface area of the solid by altering the particle size (e.g., with micronization). For many drugs, reducing the particle size reduces the dose needed to achieve the same therapeutic effect. The particle size reduction increases the specific surface area and the dissolution rate and does not affect solubility.

The rate of dissolution may also be altered by choosing a suitable

polymorph
of a compound. Different polymorphs have different solubility and dissolution rate characteristics. Specifically, crystalline forms dissolve slower than amorphous forms since they require more energy to leave the lattice during dissolution. The stablest crystalline polymorph has the lowest dissolution rate. Dissolution also differs between anhydrous and hydrous forms of a drug. Anhydrous forms often dissolve faster but sometimes are less soluble.

hydrolyze
these esters to release the parent drug.

Coatings on a tablet or pellet may act as barriers to reducing the dissolution rate. Coatings may also be used to control where dissolution takes place. For example,

intestines
.

Drugs held in solution do not need to be dissolved before being absorbed.

Lipid-soluble drugs are absorbed more rapidly than water-soluble drugs.[9]

Ionization

The

bloodstream. Cell membranes may act as barriers to some drugs. They are essentially lipid bilayers which form semipermeable membranes. Pure lipid bilayers are generally permeable only to small, uncharged solutes. Hence, whether or not a molecule is ionized will affect its absorption, since ionic molecules are charged. Solubility favors charged species, and permeability favors neutral species. Some molecules have special exchange proteins and channels to facilitate movement from the lumen into the circulation.[vague
]

Ions cannot passively diffuse through the gastrointestinal tract because the epithelial cell membrane is made up of a

phospholipid bilayer
, comprising two layers of phospholipids in which the charged hydrophilic heads face outwards and the uncharged hydrophobic fatty acid chains are in the middle of the layer. The fatty acid chains repel ionized, charged molecules. This means that the ionized molecules cannot pass through the intestinal membrane and be absorbed.

The

weak acids (such as aspirin) will be present mainly in their non-ionic form, and weak bases will be in their ionic form. Since non-ionic species diffuse more readily through cell membranes, weak acids will have a higher absorption in the highly acidic stomach
.

However, the reverse is true in the basic environment of the intestines—weak bases (such as caffeine) will diffuse more readily since they will be non-ionic.

This aspect of absorption has been targeted by medicinal chemists. For example, they may choose an

pharmacodynamic
properties of a drug.

The solubility and permeability of a drug candidate are important physicochemical properties the scientist wants to know as early as possible.[10]

Other factors

Absorption also varies depending on bioactivity, resonance, the inductive effect, isosterism, bio-isosterism, and consideration, amongst others.

Types

Types of absorption in pharmacokinetics include the following:[11]

  • Instantaneous absorption: absorption is nearly immediate. A common example is bolus
    intravenous injection
    .
  • Zero-order absorption: rate of absorption is constant. A common example is continuous
    intravenous infusion
    .
  • First-order absorption: rate of absorption is proportional to the amount of drug remaining to be absorbed. Representative examples include typical cases of
    subcutaneous injection, and intramuscular injection
    .

See also

References

  1. .
  2. .
  3. ^ LE.JENNIFER (2020-03-27). "Drug Absorption - Clinical Pharmacology". MSD Manual Professional Edition. Retrieved 2020-03-28.
  4. ^ Kaplan Pharmacology 2010, page 6, Absorption
  5. ^ Kaplan Pharmacology 2010, Video Lectures, Absorption chapter
  6. ^ Shimizu, Shinya. "Routes of administration" (PDF). The Laboratory Mouse. 1: 527–543.
  7. ^ Jean, Kim; Orlando, Jesus. "Medication Routes of Administration". StatPearls Publishing. 1: 121–141.
  8. S2CID 22893348
    .
  9. .
  10. . Retrieved 21 July 2021.
  11. .

Further reading

External links