What are the three factors that affect drug absorption?

October 14, 2025 •

5 min read

The bioavailability of an orally administered drug is often less than 100% due to incomplete absorption and first-pass metabolism [1.5.3]. Understanding what are the three factors that affect drug absorption—the drug's properties, the patient's physiology, and the administration route—is crucial in pharmacology.

Quick Summary

Drug absorption is influenced by three main categories of factors: those related to the drug itself (e.g., solubility), patient-specific variables (e.g., age, GI health), and the route of administration (e.g., oral, IV).

Key Points

Drug Properties: A drug's solubility, particle size, and chemical form (pKa, salt vs. free acid) are fundamental to its ability to dissolve and cross biological membranes [1.3.3].
Patient Factors: Age, GI health (pH, motility), the presence of food, and underlying diseases can significantly alter the rate and extent of drug absorption [1.4.3].
Administration Route: The route (e.g., oral, IV, transdermal) dictates whether the drug is subject to absorption barriers and the first-pass effect, directly impacting its bioavailability [1.5.1].
Bioavailability: This term represents the fraction of an administered drug that reaches the systemic circulation; it is 100% for IV drugs but often much lower for oral drugs [1.5.3, 1.6.1].
First-Pass Effect: Orally administered drugs pass through the liver before entering systemic circulation, where a significant portion may be metabolized and inactivated, reducing bioavailability [1.9.1].
pH-Partition Hypothesis: This theory explains that unionized, lipid-soluble forms of weak acid or base drugs are more readily absorbed across lipid membranes [1.3.5].
Food Interactions: Food can delay, reduce, or sometimes increase drug absorption by altering GI conditions or by direct binding [1.2.6].

Drug absorption is the process by which a drug moves from its site of administration into the systemic circulation [1.7.1]. This process is a cornerstone of pharmacokinetics and is critical for a drug to exert its therapeutic effect. The rate and extent of absorption determine the drug's bioavailability—the fraction of the administered dose that reaches the bloodstream unchanged [1.7.1]. While an intravenous (IV) injection provides 100% bioavailability by definition, other routes, especially oral administration, face numerous hurdles [1.5.1, 1.6.1]. The efficiency of this process is governed by a complex interplay of variables that can be broadly categorized into three main groups.

Factor 1: Drug-Related (Physicochemical) Properties

The inherent physical and chemical properties of a drug are primary determinants of its ability to be absorbed [1.3.3]. These properties dictate how the drug interacts with the body's biological membranes.

Key Physicochemical Properties:

Solubility & Dissolution Rate: Before a drug can be absorbed, it must first dissolve in the body's fluids. Hydrophilic (water-soluble) drugs dissolve easily but may struggle to cross lipid-rich cell membranes, whereas lipophilic (lipid-soluble) drugs cross membranes easily but may have poor dissolution [1.3.1]. A balance, known as the partition coefficient (log P), is often ideal for oral absorption [1.3.5].
Particle Size and Surface Area: Smaller drug particles have a larger surface area, which generally leads to a faster dissolution rate and, consequently, faster absorption [1.3.5]. Techniques like micronization are used to reduce particle size and improve the bioavailability of poorly soluble drugs like griseofulvin [1.3.5].
Ionization (pKa): Most drugs are weak acids or weak bases, existing in both ionized and unionized forms. The unionized form is more lipid-soluble and is preferentially absorbed via passive diffusion [1.3.3]. The pH of the surrounding environment (e.g., the acidic stomach vs. the more alkaline intestine) determines the degree of ionization, as described by the pH-partition hypothesis [1.3.5].
Chemical Form (Salts, Esters): Converting a drug into a salt form is a common strategy to increase its solubility and dissolution rate [1.3.5]. For example, sodium salts of weak acids often dissolve more readily than the free acid form. Conversely, some ester forms (prodrugs) are designed to be more lipid-soluble to enhance absorption, later converting to the active drug within the body [1.3.3].
Crystal Structure (Polymorphism): Some drugs can exist in different crystalline structures, known as polymorphs, or in a non-crystalline amorphous form. Amorphous and metastable polymorphs are generally more soluble and have faster dissolution rates than stable crystalline forms [1.3.5].

Factor 2: Patient-Related (Physiological) Factors

The individual characteristics of the patient significantly influence how a drug is absorbed. These factors can vary widely from person to person and even within the same person over time [1.4.1, 1.4.3].

Important Patient Characteristics:

Age: Physiological differences in infants and the elderly affect absorption. Infants may have higher gastric pH, while elderly individuals might experience decreased intestinal blood flow, altered gastric emptying, and a higher incidence of achlorhydria (low stomach acid) [1.4.3].
Gastrointestinal (GI) Motility: The speed at which contents move through the GI tract affects absorption. Very fast transit (e.g., diarrhea) can reduce the time available for absorption [1.2.6]. Conversely, delayed gastric emptying can slow the onset of action for drugs primarily absorbed in the intestine [1.4.3].
GI pH: The pH varies along the GI tract, from highly acidic in the stomach (pH 1-3) to more neutral in the small intestine (pH 6-8) [1.3.1]. This affects a drug's ionization and stability. Conditions like achlorhydria can impair the absorption of drugs that require an acidic environment to dissolve [1.2.4].
Presence of Food: Food can affect drug absorption in multiple ways. It can delay gastric emptying, alter GI pH, stimulate bile secretion (which can enhance the absorption of lipophilic drugs), and directly bind to drugs, forming unabsorbable complexes [1.2.5, 1.2.6]. For example, tetracycline absorption is reduced by dairy products [1.3.1].
Blood Flow to the Absorption Site: Higher blood flow at the absorption site maintains a steep concentration gradient, facilitating faster absorption. Blood flow to the GI tract increases after a meal [1.4.3]. For topical applications, circulation to the skin is a key factor [1.2.1].
Disease States: GI diseases like Crohn's disease or celiac disease can reduce the available surface area for absorption [1.4.2]. Cardiovascular diseases can reduce blood flow to the gut, and liver diseases can impact the first-pass effect [1.4.3].

Factor 3: Route of Administration

The method chosen to deliver a drug into the body is a critical factor that directly controls its bioavailability [1.5.1].

Comparison of Administration Routes


Route	Bioavailability	Onset of Action	Key Considerations
Intravenous (IV)	100% [1.5.1]	Immediate [1.5.3]	Bypasses absorption entirely. Useful for emergencies and poorly absorbed drugs.
Oral (PO)	Variable (Often <100%) [1.5.3]	Slower (30-90 min)	Subject to the first-pass effect, where the liver metabolizes the drug before it reaches systemic circulation [1.5.1, 1.9.1]. Affected by all drug and patient factors.
Sublingual/Buccal	High	Rapid	Bypasses the first-pass effect as blood drains directly into the superior vena cava [1.5.5].
Intramuscular (IM)	High (60-100%) [1.5.3]	Slower than IV	Absorption rate depends on blood flow to the muscle. Can be used for depot injections providing slow, sustained release [1.5.4].
Subcutaneous (SQ)	High	Variable	Slower than IM. Absorption can be affected by local factors like tissue fat and blood flow [1.5.5].
Rectal	Variable (Approx. 50% bypasses first-pass) [1.5.5]	Variable	Useful when oral route is not feasible. Absorption can be irregular.
Transdermal	Variable	Slow	Provides sustained delivery and bypasses first-pass effect. Requires adequate skin perfusion and subcutaneous fat [1.2.1].

The First-Pass Effect

For orally administered drugs, a significant portion is absorbed from the GI tract and transported via the portal vein directly to the liver. The liver is a major site of drug metabolism [1.9.3]. This process, known as the first-pass effect or first-pass metabolism, can inactivate a substantial amount of the drug before it ever reaches the systemic circulation, thereby reducing its bioavailability [1.9.1]. Drugs like propranolol and lidocaine experience a significant first-pass effect, which is why their oral doses are much higher than their IV doses [1.9.3].

Conclusion

In summary, drug absorption is a complex process influenced by the drug's own physicochemical properties, the unique physiological state of the patient, and the chosen route of administration. A thorough understanding of these three intertwined factors is essential for healthcare professionals to optimize drug therapy, ensuring maximum efficacy while minimizing potential adverse effects. By considering how a drug will dissolve, permeate membranes, and navigate the body's systems, clinicians can make informed decisions on dosing and administration to achieve the desired therapeutic outcome.

Authoritative Link: For more in-depth information on drug absorption, visit the MSD Manual.

Frequently Asked Questions

The bioavailability of an oral drug is often less than 100% due to two main reasons: incomplete absorption in the gastrointestinal tract and the 'first-pass effect,' where the drug is metabolized by the liver before it can enter the systemic circulation [1.5.1, 1.5.3].

The first-pass effect (or first-pass metabolism) is a phenomenon where a drug's concentration is significantly reduced after it is absorbed from the gut and passes through the liver via the portal vein. Liver enzymes metabolize the drug, decreasing the amount of active drug that reaches the rest of the body [1.9.1, 1.9.3].

Food can affect drug absorption by delaying stomach emptying, changing the pH of the stomach, increasing blood flow to the gut, and sometimes binding directly to the drug, which can either increase, decrease, or delay its absorption [1.2.5, 1.2.6].

Yes, age is a significant factor. Infants have different gastric pH and intestinal function compared to adults. The elderly may have decreased blood flow to the gut, slower gastric emptying, and other physiological changes that can alter drug absorption patterns [1.4.3].

Medications are given sublingually to allow for rapid absorption directly into the bloodstream through the rich blood supply under the tongue. This route bypasses the gastrointestinal tract and the liver, thus avoiding the first-pass effect and leading to higher bioavailability [1.5.5].

For a drug to be absorbed, it must first dissolve in the fluids of the GI tract. Its lipid solubility then determines how well it can pass through the lipid-based cell membranes. An ideal drug has a good balance of both water and lipid solubility for optimal absorption [1.3.1, 1.3.5].

Drug absorption is the process of a drug moving from the site of administration to the bloodstream [1.7.2]. Bioavailability is the outcome of that process; it is the fraction or percentage of the administered drug that actually reaches the systemic circulation in an unchanged, active form [1.6.2].