INTRODUCTION
Before isotretinoin, no other acne therapy targeted all four pathogenesis factors of acne (including hyper-keratinization, sebum production, Cutibacterium acnes proliferation, and inflammation).1,2 Rather, other non-isotretinoin treatments for acne are often used in combination to address multiple aspects of acne pathogenesis at once.3 Isotretinoin, available in the US for almost four decades, is an oral retinoid recommended as a first-line treatment option for treating severe nodular acne.3 In addition to severe nodular acne, oral isotretinoin is used for the treatment of moderate acne that is treatment-resistant or for the management of acne that causes physical scarring or psychosocial distress, or both.3 Over time, oral isotretinoin has revolutionized the management of severe and recalcitrant acne patients due to its ability to markedly induce acne clearance coupled with its ability to achieve prolonged remission.4,5 Isotretinoin is the only treatment for which a single course of therapy has demonstrated complete or near-complete clearance of acne lesions and prolonged remission in the majority of patients with severe recalcitrant nodular acne.4,5
Although traditional oral isotretinoin has transformed acne management, its administration has faced several challenges. Notably, the bioavailability of traditional oral isotretinoin is variable and highly dependent on food administration. Isotretinoin, like other vitamin A derivatives, is a highly lipophilic molecule and its absorption is enhanced by a high-fat meal.6-8 Because of this, maximal absorption of traditional isotretinoin depends on consumption of a high-fat, high calorie meal. Pharmacokinetics of traditional isotretinoin were performed with a standardized high-fat, high-calorie meal containing 50 grams of fat and 800 to 1000 calories.7,9 FDA guidance in 2002 recommended this test meal should derive approximately 150, 250, and 500 to 600 calories from protein, carbohydrates, and fat, respectively.9 When taking traditional isotretinoin without a high-fat meal, fasting isotretinoin plasma levels can be 60 percent lower than fed conditions.8 Furthermore, peak plasma concentrations of traditional oral isotretinoin between fed and fasted conditions can vary by a factor of nearly threefold, which may potentially affect both efficacy and safety.6
Although traditional oral isotretinoin has transformed acne management, its administration has faced several challenges. Notably, the bioavailability of traditional oral isotretinoin is variable and highly dependent on food administration. Isotretinoin, like other vitamin A derivatives, is a highly lipophilic molecule and its absorption is enhanced by a high-fat meal.6-8 Because of this, maximal absorption of traditional isotretinoin depends on consumption of a high-fat, high calorie meal. Pharmacokinetics of traditional isotretinoin were performed with a standardized high-fat, high-calorie meal containing 50 grams of fat and 800 to 1000 calories.7,9 FDA guidance in 2002 recommended this test meal should derive approximately 150, 250, and 500 to 600 calories from protein, carbohydrates, and fat, respectively.9 When taking traditional isotretinoin without a high-fat meal, fasting isotretinoin plasma levels can be 60 percent lower than fed conditions.8 Furthermore, peak plasma concentrations of traditional oral isotretinoin between fed and fasted conditions can vary by a factor of nearly threefold, which may potentially affect both efficacy and safety.6
