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

Abstract

Background:

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.

Objective:

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.

Methods:

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 via octanol/water and chloroform/water distribution coefficients (logD) at pH 3.5, 5.5, and 7.4.

Results:

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.

Conclusion:

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.

• Authors: Ayman Grada, James Q Del Rosso, Angela Y Moore, Linda Stein Gold, Julie Harper, Giovanni Damiani, Katharina Shaw, Sabine Obagi, Raidah J Salem, S Ken Tanaka, Christopher G Bunick
• Journal: Frontiers in medicine (Front Med (Lausanne)) Vol. 9 Pg. 1033980 ( 2022) ISSN: 2296-858X [Print] Switzerland
• PMID: 36569144 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Grada, Del Rosso, Moore, Stein Gold, Harper, Damiani, Shaw, Obagi, Salem, Tanaka and Bunick.