The great advantage of topical therapy is that the drugs are delivered straight to where they are needed, at an optimum concentration for the target organ. Systemic side effects from absorption are less than those expected from the same drug given systemically. With topical treatment, vital organs such as the marrow, liver and kidneys are exposed to lower drug concentrations than is the skin. However, topical treatment is often messy, time-consuming and incomplete, whereas systemic treatment is clean and quick and its effect is uniform over the entire skin surface. Cost must also be considered.

Some drugs can only be used topically (e.g. permethrin for scabies and mupirocin for bacterial infections), while others only work systemically (e.g. azathioprine for pemphigus and methotrexate for psoriasis).

When a choice exists, and both possibilities are equally effective, then local treatment is usually to be preferred. Most cases of mild pityriasis versicolor, for example, respond to topical antifungals alone so systemic itraconazole is not the treatment of first choice.

A drug (the active ingredient) used on the skin must be dissolved or suspended in a vehicle (base). The choice of the drug and of the vehicle are both important and depend on the diagnosis and the state of the skin. For a drug to be effective topically, it must pass the barrier to diffusion presented by the horny layer (see Chapter 2). This requires the drug to be transferred from its vehicle to the horny layer, from which it will diffuse through the epidermis into the papillary dermis. Passage through the horny layer is the rate-limiting step.

The transfer of a drug from its vehicle to the horny layer depends on its relative solubility in each (measured as the partition coefficient). Movement across the horny layer depends both upon the concentration gradient and on restricting forces (its diffusion constant). In general, non-polar substances penetrate more rapidly than polar ones. Low molecular weight drugs penetrate the epidermis better than high molecular weight ones. A rise in skin temperature and in hydration, both achieved by covering a treated area with polyethylene occlusion, encourages penetration.

Some areas of skin present less of a barrier than do others. Two extreme examples are palmar skin, with its impermeable thick horny layer, and scrotal skin, which is thin and highly permeable. The skin of the face is more permeable than the skin of the body. Body fold skin is more permeable than nearby unoccluded skin. In humans, absorption through the hair follicles and sweat ducts is of little significance and the amount of hair on the treated site is no guide to its permeability.

In many skin diseases, the horny layer becomes abnormal and loses some of its barrier function. For example, the abnormal nucleated (parakeratotic) horny layers of psoriasis and chronic eczema, although thicker than normal, have lost much of their protective qualities. Water loss is increased and therapeutic agents penetrate more readily. Similarly, breakdown of the horny layer by chemicals (e.g. soaps and detergents) and by physical injury will allow drugs to penetrate more easily. Conversely, as the skin heals,the barrier function of the horny layer returns and drug absorption diminishes. In summary, the penetration of a drug through the skin depends on the following factors:

• Molecular weight;
  
• Concentration;
  
• Base;
  
• Partition coefficient;
  
• Diffusion constant;
  
• Thickness of the horny layer;
  
• State, including hydration, of the horny layer; and
  
• Temperature.