Drug Administration Routes and Absorption Sites

Drug Administration Pathways

Enteral Routes (Oral Administration)

These routes involve administration through the gastrointestinal tract:

• Oral Mucosa: Primarily a passage for drugs during swallowing, not a significant absorption site.
• Esophageal Mucosa: Minimal absorption occurs during transit.
• Stomach Mucosa: Limited absorption. The acidic pH (2.5-3.5) favors the absorption of weak acids (pKa > 2). Absorption depends on the drug's pKa.
• Intestinal Mucosa (Small Intestine): Major site of absorption due to its very large surface area (villi) and high vascularization. The basic pH (5-8) favors the absorption of weak bases (pKa < 9).
• Large Intestine Mucosa: Less absorption compared to the small intestine and stomach. Alkaline pH. Primarily absorbs water, electrolytes, and some glucose. Acts as a reserve area and site of biotransformation by bacterial flora.

Parenteral Routes

These routes bypass the gastrointestinal tract:

Intravascular Administration

Intravenous (IV)

• Administered as a bolus (single dose) or infusion (phleboclysis).
• Provides an immediate effect, preferred for acute conditions.
• Requires sterile equipment and administration by a health professional.
• Typically uses aqueous, non-pyrogenic, isotonic solutions.
• Achieves 100% bioavailability, bypassing the first-pass effect.

Intra-arterial (IA)

• Similar requirements and characteristics to IV administration but delivers the drug directly into a specific artery, targeting a particular organ or tissue.

Extravascular Administration

Intramuscular (IM)

• Injected into muscle tissue, preferably large, well-vascularized muscles.
• Bioavailability is greater than enteral routes but less than intravenous.
• Solutions can be aqueous or non-aqueous (e.g., oily depots).
• Absorption rate can be increased by massage or heat application.

Subcutaneous (SC) / Intradermal (ID)

• Subcutaneous: Injected into the fatty tissue beneath the skin. Absorption is generally slower than IM, relying on simple diffusion, and is greater for soluble drugs. Suitable for sustained release formulations.
• Intradermal: Injected into the dermis (top layer of skin). Used for specific purposes like allergy testing, tuberculin tests, or some vaccines. Very small volumes are administered.

Inhalation

• Administered via the respiratory tract.
• Pharmaceutical forms include gases, volatile liquids, aerosols, smoke, and fine powders (dry powder inhalers).
• Offers a very large absorption surface area (alveoli).
• Rich blood supply leads to rapid absorption into systemic circulation.
• Bypasses the first-pass effect.

Topical and Other Routes

Local Application

Skin (Dermal/Cutaneous)

• Applied directly to the skin surface.
• Absorption and effect depend heavily on the drug's properties, the vehicle (dosage form like creams, ointments, gels, patches), and skin condition.
• Usually intended for local effects (e.g., treating skin conditions, inflammation, muscle/joint pain). Transdermal patches are designed for systemic effects.

Mucous Membranes (Conjunctival, Nasal, Vaginal)

• Applied to specific mucous membranes (eye, nose, vagina).
• These areas are well-vascularized, favoring absorption, but are primarily used for local treatment of conditions affecting these membranes (e.g., eye drops for glaucoma, nasal sprays for congestion, vaginal creams for infections).
• Requires soluble drugs, often in low doses due to potential systemic absorption.

Topical Application for Systemic Effects

Sublingual Mucosa

• Drug placed under the tongue for absorption into systemic circulation.
• The mucosa is thin and highly vascularized, allowing rapid absorption directly into the capillary network draining into systemic veins.
• Bypasses the first-pass effect (liver metabolism).
• Useful for achieving rapid systemic effects and avoids drug destruction by stomach acid or enzymes.

Rectal Mucosa

• Administered via the rectum (suppositories, enemas) for local or systemic effects.
• Highly vascularized area allows for relatively rapid and significant absorption.
• Partially bypasses the first-pass effect (lower rectal veins drain directly into systemic circulation, while upper veins drain to the portal vein).
• Useful when oral administration is difficult or contraindicated (e.g., unconsciousness, nausea/vomiting, pediatric patients).

Understanding the First-Pass Effect

The first-pass effect (also known as first-pass metabolism or presystemic metabolism) refers to the process where a drug administered orally is absorbed from the gastrointestinal tract and transported via the portal vein directly to the liver. In the liver, the drug may undergo significant metabolism before it reaches the systemic circulation. This metabolization reduces the concentration (bioavailability) of the active drug reaching the rest of the body. All parenteral routes (intravenous, intramuscular, subcutaneous, etc.), as well as sublingual and significantly rectal administration, bypass or partially bypass this initial hepatic metabolism, leading to higher bioavailability compared to the oral route for susceptible drugs.