Principles of Topical Therapy at a Glance
- The efficacy of a topically applied drug depends on its inherent potency and on its ability to penetrate skin.
- Some factors that affect penetration include: concentration of medication, thickness and integrity of the stratum corneum, frequency of application, occlusiveness of the vehicle, and compliance.
- Topical formulations (vehicles) are meant to enhance the beneficial effects of the medication.
- Either the vehicle or its active ingredient(s) may cause local toxicity.
- Topical medications may induce systemic toxicity.
Sensible topical drug therapy involves not only the selection of an appropriate agent, but also a thoughtful consideration of the areas of the body affected, the state of the diseased skin, the concentration of the drug, the type of vehicle (e.g., ointment, cream, lotion), the method of application, and a defined duration of use that both maximizes efficacy and minimizes adverse side effects. Behind each of these considerations are basic principles that help guide the practitioner toward a rational plan of therapy.
The therapeutic efficacy of a topical drug relates to both its inherent potency and the ability of that drug to penetrate the skin.1 In fact, many potent agents, such as hydrocortisone and fluocinolone acetonide, are quite poorly absorbed after topical application. Conversely, many well-absorbed agents with weak potency have negligible therapeutic use. Percutaneous absorption necessitates passage through the stratum corneum, epidermis, papillary dermis, and into the bloodstream. (See Chapter 215 for information on the pharmacokinetics of topical therapy.)
In contrast to many orally administered drugs that are nearly completely absorbed within a few hours, topical medicines generally have a poor total absorption and a very slow rate of absorption. For example, less than 2% of a topically applied corticosteroid such as hydrocortisone is absorbed after a single application left on the skin for more than 1 day. Furthermore, peak rates of absorption are reached up to 12–24 hours after application. Fortunately, low absorption does not necessarily translate into low efficacy. Drugs such as topical corticosteroids are effective because of their inherent potency and can exert clinically significant effects in spite of low absorption. In this light, absorption represents only one of many facets of efficacy.
The stratum corneum is the rate-limiting barrier to percutaneous drug delivery. This cornified layer is composed of ceramides, free fatty acids, and cholesterol in a 1:1:1 molar ratio. By weight, the stratum corneum consists of 50% ceramides (acylceramides being the most abundant), 35% cholesterol, and 15% free fatty acids. The stratum corneum thickness and, thus, drug penetration will vary depending on body site.2 Box 214-1 lists varying body sites and their relative resistance to percutaneous absorption.
Box 214-1 Regional Differences in Penetrationa