Are topical creams absorbed systemically? The surprising truth about skin absorption

Research indicates that active ingredients in topical creams can be absorbed systemically, contrary to the belief that these medications only act locally. The extent of this absorption depends on the medication's characteristics, skin condition, and application method.

Quick Summary

Topical creams can be absorbed into the systemic circulation. Absorption depends on the drug, formulation, application area, and skin integrity. This can lead to unintended systemic side effects, particularly with potent medications like corticosteroids. Understanding the factors involved is crucial for safe medication use.

Key Points

• Systemic Absorption is Possible: Active ingredients in topical creams can and do get absorbed into the bloodstream, a process known as percutaneous absorption.

• Skin Barrier is Not Impenetrable: While the skin's outermost layer acts as a barrier, its integrity and thickness vary, allowing some drugs to pass through, especially on compromised or thin skin.

• Factors Influence Absorption: Absorption is affected by the drug's properties (size, fat-solubility), the application site, the use of occlusive dressings, and the patient's age.

• Potent Medications are Higher Risk: Potent drugs like corticosteroids can cause significant systemic side effects, such as adrenal suppression, with prolonged or extensive use.

• Formulation Matters: The vehicle (e.g., ointment vs. cream vs. gel) significantly impacts the rate and amount of absorption. Ointments are more occlusive and can increase absorption compared to creams or gels.

• Minimize Risk with Proper Use: Following medical advice, using the lowest effective dose, avoiding large application areas, and not using occlusive dressings excessively can help minimize systemic absorption risks.

Understanding the Skin's Barrier

The skin is the body's largest organ and serves as a primary protective barrier against external substances, including medications. The outermost layer, the stratum corneum, is particularly responsible for this barrier function. It is composed of flattened, dead skin cells embedded in a matrix of lipids. This unique 'brick and mortar' structure effectively limits the penetration of most substances. However, this barrier is not impenetrable, and certain conditions and drug properties can significantly alter its permeability, allowing medications to pass through the epidermis and dermis to reach the bloodstream.

How drugs penetrate the skin

Drugs can penetrate the skin through two main routes: the transcellular (through the cells) and paracellular (between the cells) pathways. The physicochemical properties of the drug determine which route is most effective. Typically, small, lipophilic (fat-soluble) molecules have a higher chance of penetrating the lipid-rich stratum corneum and getting absorbed.

Key Factors Influencing Systemic Absorption

Several factors can increase or decrease the risk of a topical medication being absorbed systemically:

• Drug properties: Molecular size, lipophilicity, and drug concentration are key determinants. Smaller, more lipid-soluble molecules penetrate the skin more readily. Higher concentrations also generally increase absorption.
• Formulation (Vehicle): The base of the product—whether it's an ointment, cream, lotion, or gel—significantly impacts absorption. Ointments are highly occlusive and can enhance absorption, while creams and lotions are less so.
• Skin Condition: Damaged, inflamed, or compromised skin, such as from burns, abrasions, or conditions like psoriasis or atopic dermatitis, has increased permeability and allows for greater absorption.
• Application Site: The thickness of the stratum corneum varies across the body. Thinner areas like the face, scalp, and scrotum are more permeable than thicker areas like the palms and soles.
• Occlusion: Covering the application area with a dressing or clothing traps moisture and increases hydration, significantly enhancing absorption. This is why occlusive dressings are used strategically for specific treatments but increase risk for systemic effects.
• Patient's Age: Infants and young children are more susceptible to systemic effects due to their larger body surface area-to-weight ratio and less mature skin barrier.

Medications with Significant Systemic Potential

While many topical products are designed for local action, certain classes of drugs are known to have significant systemic absorption potential, especially with improper use.

Corticosteroid Creams

Potent topical corticosteroids are a classic example of medications that can be absorbed systemically in clinically significant amounts. Prolonged and widespread use can lead to systemic side effects, including:

• Adrenal Suppression: The body's adrenal glands may stop producing natural steroid hormones due to negative feedback.
• Cushing's Syndrome: Characterized by symptoms like a rounded face, central obesity, and skin thinning.
• Hyperglycemia: Increased blood sugar levels.
• Growth Suppression: A particular risk in children.

Topical Pain Relievers (NSAIDs)

Topical Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in gels or compounded creams can also be absorbed systemically. This is particularly concerning for individuals already taking oral NSAIDs, as the combined systemic dose could increase the risk of adverse reactions, such as stomach issues or kidney problems.

Other Agents

Historically, agents like salicylic acid, boric acid, and hexachlorophene have been associated with systemic toxicity when used excessively on compromised skin. Transdermal patches are specifically engineered for systemic delivery and serve as a reminder that the skin is a viable route for systemic medication.

Formulations and Absorption: A Comparison

To illustrate how the vehicle of a topical medication affects its absorption characteristics, consider the following comparison:

Property	Ointment	Cream	Gel	Lotion
Base Composition	Primarily oil/petroleum jelly-based	Emulsion of oil and water	Water-based, often with alcohol	Thin emulsion of oil and water
Occlusiveness	Highest; forms a barrier	Moderate	Lowest; non-occlusive	Low
Absorption Rate	Slowest; stays on skin longer	Moderate; absorbs faster than ointment	Fastest; dries quickly	Fast
Primary Use	Very dry, thick, or damaged skin; provides high hydration	General moisturizing and medication delivery	Oily or hairy skin; cooling effect	Large areas of skin; lightweight

How to Minimize Systemic Absorption and Associated Risks

For most standard topical creams intended for local effect, a minimal amount of systemic absorption is normal and typically not harmful. However, for potent medications or high-risk patients, the following steps can reduce the risk of unintended systemic effects:

1. Use the lowest effective dose: Apply the minimal amount necessary to cover the affected area.
2. Avoid prolonged or widespread use: Limit the duration of treatment, especially for potent medications. Avoid applying to large areas of the body.
3. Refrain from occlusive dressings: Unless specifically instructed by a doctor, do not cover treated areas with bandages or plastic wraps, as this can trap heat and moisture, significantly increasing absorption.
4. Be cautious with broken skin: Avoid applying potent topicals to open wounds, burns, or severely inflamed skin, where the barrier function is compromised.
5. Follow doctor's instructions: Always follow the precise directions given by a healthcare professional, including the frequency and duration of application.
6. Consider medication holidays: For certain chronic conditions treated with potent medications like corticosteroids, a doctor may recommend periodic breaks from treatment to reduce the risk of systemic effects.
7. Inform your doctor of all medications: This includes other topical products, as drug interactions can occur, and systemic exposure from multiple sources can add up.

Conclusion

The question, "Are topical creams absorbed systemically?", has a clear answer: yes, they can be, though the degree of absorption is highly variable. While most topical products pose minimal systemic risk for healthy individuals when used correctly, factors like drug potency, formulation, application site, and skin integrity can dramatically increase absorption. Awareness of these variables is crucial, especially for vulnerable populations and when using potent medications like corticosteroids or NSAIDs. Always consult a healthcare provider for guidance on managing topical treatments to ensure both local effectiveness and systemic safety. For more information on drug development and systemic considerations for topical medications, the National Center for Biotechnology Information (NCBI) offers numerous resources.

Frequently Asked Questions

Can over-the-counter topical creams be absorbed systemically?

Yes, even over-the-counter (OTC) topical creams can be absorbed systemically, though the amount is typically small. Examples include certain topical pain relievers or antiseptics. It's important to use them as directed and be aware of potential risks, especially with prolonged use.

Are children at a higher risk for systemic absorption from topical creams?

Yes, infants and young children are more vulnerable to systemic absorption and its adverse effects. This is due to their higher body surface area to body weight ratio and the relative immaturity of their skin barrier.

What is the difference between a topical cream and a transdermal patch?

A topical cream is generally designed for a local effect, while a transdermal patch is specifically engineered for systemic delivery, with active ingredients intended to enter the bloodstream in controlled amounts.

Can I get systemic side effects from topical corticosteroids?

Yes, especially with high-potency corticosteroids used over large areas or for extended periods. Potential systemic side effects include adrenal suppression, Cushing's syndrome, and increased blood sugar levels.

How does broken or inflamed skin affect systemic absorption?

Compromised skin, such as from burns, eczema, or cuts, has a weakened barrier function. This significantly increases the permeability and, consequently, the systemic absorption of applied medications.

Does the area of the body where I apply cream matter for absorption?

Yes, it does. Skin permeability varies by body part. Thinner skin areas like the face, scalp, and scrotum are more permeable and prone to higher absorption than thicker skin on the palms and soles.

Can using an occlusive dressing increase systemic absorption of topical creams?

Yes, using an occlusive dressing, such as a bandage or plastic wrap, significantly enhances drug penetration by hydrating the stratum corneum and increasing temperature, thereby increasing systemic exposure.