Absorption and its pharmacokinetic role
Absorption (absorptio, from Latin absorbeo — to absorb) is a crucial step that ensures the transfer of a medication from its initial site of contact with tissues directly into the internal environment. This process begins immediately after the patient takes the drug.
The chosen delivery route dictates the fundamental pharmacokinetic parameters of therapy:
- Absorption rate — determines how quickly the expected therapeutic effect will occur.
- Extent of absorption (bioavailability) — accounts for the fraction of the original substance that reaches the target, thereby determining the overall magnitude of the effect.
- Duration of action — indicates how long the therapeutic effect on the body will persist.
Classification of administration routes
The fundamental classification of all delivery methods is based on a single criterion: whether the drug passes through the gastrointestinal tract (GIT) or bypasses it.
Enteral routes
The group name (enteralis) comes from the Greek roots ento (inside) and enteron (intestine). This approach involves administering drugs through various parts of the digestive system. The main types include:
- Oral (per os) — classic swallowing of the drug.
- Sublingual (sublingualis) — placing the formulation under the tongue.
- Transbuccal (transbuccalis) — applying or placing the drug on the oral mucosa inside the cheek.
- Rectal (per rectum) — administering the medication via the rectum.
Parenteral routes
The second major group comprises methods (parenteralis) in which the substance is delivered into the body bypassing the digestive tract. These include inhalations, transdermal applications, and various injections:
- Intravenous (intravenosa).
- Intraarterial (intraarterialis).
- Intramuscular (intramuscularis).
- Subcutaneous (subcutanea).
- Intraperitoneal (intraperitonealis).
- Intrasternal (into the cancellous bone of the sternum).
- Intrathecal (subarachnoid or epidural administration).
Physicochemical properties and barriers
The choice of administration route is inextricably linked to the physicochemical properties of the molecule, primarily its polarity and solubility. Understanding these characteristics is critical for formulating a proper dosage form.
For a substance to be absorbed in the intestine, it must first dissolve in the liquid contents (the aqueous chyme). To reach the epithelial surface, the molecule requires hydrophilicity. However, enterocyte membranes consist of a lipid bilayer. To cross this barrier via passive diffusion, the molecule must possess lipophilicity. An ideal drug has an optimal balance of these two properties.
Pharmacologists often use salt formation: administering weak acids and bases as salts sharply increases their water solubility, thereby significantly improving bioavailability.
Effect of pH on absorption
The pH of the environment in which the drug ends up plays a decisive role in successful absorption. According to the Henderson-Hasselbalch equation, the degree of ionization of a molecule changes depending on the acidity of the surrounding space.
The main rule of absorption states that exclusively the non-ionized (i.e., lipophilic) fraction of the drug easily penetrates cellular barriers. Ionized molecules are retained on the membrane surface and cannot pass into the cell via simple diffusion.
Briefly: answers to topical questions
What are the pros and cons of the oral route of administration?
The oral route of administration (per os) has several advantages, but it also has significant drawbacks.
Pros:
- Convenience — physiological, simple for the patient, does not require sterility or medical personnel.
Cons:
- Slow absorption — the effect does not occur immediately.
- Degradation — partial inactivation in the gastrointestinal tract and liver (first-pass effect).
- Variability of effect — depends on intestinal motility, mucosal condition, environmental pH, and chyme composition.
- Interaction — risk of interaction with food and other drugs.
What are the mechanisms of drug absorption across cell membranes?
The absorption of drug substances across cell membranes occurs through several primary mechanisms.
- Passive diffusion (diffusio) — the main mechanism for lipophilic substances along a concentration gradient.
- Filtration (filtratio) — the passage of small water-soluble molecules through aqueous pores.
- Active transport — the transfer of substances against a concentration gradient requiring energy and specific carrier systems.
- Facilitated diffusion (diffusio facilitata) — an energy-independent process along an electrochemical gradient involving carriers.
- Pinocytosis — the engulfment of large molecules with a molecular weight exceeding 1000.
How does environmental pH affect the absorption of weak acids in the stomach?
In the acidic environment of the stomach, weak acids are predominantly in a non-ionized form, so their absorption begins. As the pH of the environment increases, the degree of their ionization rises. Ionized forms cross lipid membranes less efficiently, so the absorption of weak acids slows down.
Which solutions must categorically not be administered subcutaneously or intramuscularly?
The sources describe strict limitations only for subcutaneous administration. It is forbidden to subcutaneously administer irritating substances and hypertonic solutions; their administration can lead to tissue necrosis. Calcium chloride is cited as an example of an irritating substance. Potent vasoconstrictors, such as norepinephrine, are also associated with the risk of tissue necrosis. There is no data in the provided sources regarding solutions categorically contraindicated for intramuscular administration; it is noted that oily solutions and depot preparations can be administered intramuscularly.
What are the main pharmacokinetic differences between sublingual and oral administration?
Sublingual administration differs from oral administration in the following features:
- First-pass effect: with sublingual administration, the drug substance enters the systemic circulation directly, bypassing the liver; with oral administration, partial inactivation may occur during passage through the liver.
- Onset of action: with sublingual administration, absorption and onset of action occur rapidly; with oral administration, absorption is slower.
- GI tract influence: sublingual substances are not exposed to gastric hydrochloric acid; for oral administration, the drug must be resistant to degradation in the GI tract, and absorption depends on environmental pH, chyme composition, and food.
- Absorption area: sublingual administration is characterized by a small absorbing surface area.
The term "enteral" is easy to remember through its Greek roots: *ento* (inside) + *enteron* (intestine). Parenteral literally means "beside the intestine".
Class and exam questions
What determines the choice of a specific route of drug administration?
The choice is primarily dictated by the physicochemical properties of the active substance—its polarity and the balance of lipophilicity and hydrophilicity.
Why are weak acids and bases often produced in salt forms?
Conversion into a salt increases the solubility of the molecule in an aqueous environment. This is a prerequisite for the drug to dissolve in the intestine and reach the epithelial surface.
Which fraction of a substance crosses cell membranes better?
Only the non-ionized, lipophilic fraction of the drug easily crosses the lipid bilayer of membranes.
What else to study on this topic
- Mechanisms of absorption: passive diffusion, active transport, and pinocytosis.
- Impact of hepatic biotransformation on ultimate bioavailability.
- Pharmacokinetic parameters: clearance and volume of distribution.
- Correlation of pharmacodynamic and toxic effects with routes of administration.
- Specifics of renal drug elimination.
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