D: Dermatologicals
Group D holds the dermatologicals, the drugs used for skin disease. Most of them are applied to the skin, but D01, D05 and D10 each have a level-3 subgroup for systemic use (D01B, D05B and D10B). The agents for skin inflammation (dermatitis) in D11 also include drugs given systemically: dupilumab (D11AH05) by injection and abrocitinib (D11AH08) by mouth [1].
| Description | In plain terms | Example drug | |
|---|---|---|---|
| D01 | Antifungals for dermatological use | Terbinafine, topical (D01AE15) / terbinafine, oral (D01BA02) | |
| D02 | Emollients and protectives | moisturisers and barrier creams | Carbamide, i.e. urea (D02AE01). Most emollient bases carry no level 5 substance code: D02AC (soft paraffin and fat products) is group-level only. |
| D03 | Preparations for treatment of wounds and ulcers | Cadexomer iodine (D03AX01) / collagenase (D03BA02). Both are adjuncts: wound and ulcer care is led by dressings, offloading and debridement rather than by a drug-level standard. | |
| D04 | Antipruritics, incl. antihistamines, anesthetics, etc. | anti-itch creams and numbing agents | Lidocaine (D04AB01) / doxepin (D04AX01) |
| D05 | Antipsoriatics | Calcipotriol, combinations, i.e. with betamethasone (D05AX52) / acitretin (D05BB02) | |
| D06 | Antibiotics and chemotherapeutics for dermatological use | topical antibacterials and antivirals, not anticancer | Mupirocin (D06AX09) / imiquimod (D06BB10) |
| D07 | Corticosteroids, dermatological preparations | Mometasone (D07AC13) / hydrocortisone (D07AA02) | |
| D08 | Antiseptics and disinfectants | Chlorhexidine (D08AC02) / povidone-iodine (D08AG02) | |
| D09 | Medicated dressings | bandages impregnated with a drug | Povidone-iodine dressings (D09AA09) / chlorhexidine dressings (D09AA12). Modern silver, foam and hydrocolloid dressings have no level 5 code; D09AX (soft paraffin dressings) is group-level only. |
| D10 | Anti-acne preparations | Adapalene (D10AD03) / isotretinoin, oral (D10BA01) | |
| D11 | Other dermatological preparations | Tacrolimus, topical (D11AH01) / dupilumab (D11AH05) |
Exposure in the skin
Topical dermatological products are designed to act locally in diseased skin, ideally with minimal systemic uptake. Their systemic availability may therefore not reflect the local bioavailability in the skin. Topical doses are also small, typically 2 to 5 mg of product per cm2, so serum and urine concentrations are often undetectable with conventional assays [2].
Drug in the skin can instead be sampled directly: tape stripping measures the drug in the stratum corneum, the outermost layer of the skin, and microdialysis measures unbound drug in the inner layer of the skin (dermis) [2].
Dermal open flow microperfusion samples the interstitial fluid of the dermis continuously, and can establish bioequivalence with 20 to 30 healthy participants, far fewer than a comparative clinical endpoint study needs. Dermal physiologically based pharmacokinetic (PBPK) models describe skin permeation at or near the site of action. In 2019, the FDA approved a generic diclofenac sodium topical gel (M02AA15) for which the applicant used a PBPK model to show bioequivalence [3].
For topical corticosteroids, a pharmacodynamic measure is used instead, the skin blanching (vasoconstriction) assay described under D07 [2].
Clinical scores
Efficacy in psoriasis and eczema (atopic dermatitis) is measured with clinical scores, such as the Psoriasis Area and Severity Index (PASI) [4] and the Eczema Area and Severity Index (EASI) [5]. How these scores are modeled is described under D05 and D11.