Reduced blood-brain barrier penetration of acne vulgaris antibiotic sarecycline compared to minocycline corresponds with lower lipophilicity

• Published in: Frontiers in medicine Vol. 9; p. 1033980
• Main Authors: Grada, Ayman, Del Rosso, James Q, Moore, Angela Y, Stein Gold, Linda, Harper, Julie, Damiani, Giovanni, Shaw, Katharina, Obagi, Sabine, Salem, Raidah J, Tanaka, S Ken, Bunick, Christopher G
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 08.12.2022
• Subjects: acne vulgaris; blood-brain barrier; dizziness; lipophilicity; Medicine; minocycline; sarecycline; antibiotic; blood-brain barrier; acne vulgaris; dizziness; minocycline; lipophilicity; sarecycline
• ISSN: 2296-858X; 2296-858X
• DOI: 10.3389/fmed.2022.1033980

Vestibular side effects such as dizziness and vertigo can be a limitation for some antibiotics commonly used to treat acne, rosacea, and other dermatology indications. Unlike minocycline, which is a second-generation tetracycline, sarecycline, a narrow-spectrum third-generation tetracycline-class agent approved to treat acne vulgaris, has demonstrated low rates of vestibular-related adverse events in clinical trials. In this work, we evaluate the brain-penetrative and lipophilic attributes of sarecycline in 2 non-clinical studies and discuss potential associations with vestibular adverse events. Rats received either intravenous sarecycline or minocycline (1.0 mg/kg). Blood-brain penetrance was measured at 1, 3, and 6 h postdosing. In another analysis, the lipophilicity of sarecycline, minocycline, and doxycycline was measured octanol/water and chloroform/water distribution coefficients (logD) at pH 3.5, 5.5, and 7.4. Unlike minocycline, sarecycline was not detected in brain samples postdosing. In the octanol/water solvent system, sarecycline had a numerically lower lipophilicity profile than minocycline and doxycycline at pH 5.5 and 7.4. The reduced blood-brain penetrance and lipophilicity of sarecycline compared with other tetracyclines may explain low rates of vestibular-related adverse events seen in clinical trials.