Posted by Conventional ketamine hydrochloride solutions are acidic and hyperosmotic, limiting their tolerability for subcutaneous (SC) delivery. BB106 is a novel ketamine formulation using the multitude of sulfobutylether-beta-cyclodextrin (SBECD) anionic substitutions as ionic counterions to achieve a new ketamine–SBECD salt in solution at near-physiologic pH and isotonicity, thereby enabling SC administration. To support its development for pain and neuropsychiatric indications, nonclinical toxicology studies were conducted in rats and minipigs.
BB106 was well-tolerated in both species. No mortality or dose-limiting systemic toxicity occurred. Clinical signs were consistent with ketamine pharmacology (eg, transient ataxia) and resolved after dosing. Local site reactions were minimal, histologically mild, and reversible. No treatment-related lesions were observed in any of the systemic tissues examined (including liver, kidney, bladder, and brain). TK analyses confirmed consistent systemic exposure without accumulation. SBECD itself produced no adverse effects at the exposure levels tested.
Repeated SC bolus injections in rats for 2 weeks and continuous SC infusion in minipigs for 4 weeks demonstrated favorable local and systemic safety profiles for BB106. These findings support its feasibility as an alternative to intravenous ketamine for pain and psychiatric disorders. To our knowledge, this is the first toxicology report of SC administration of an SBECD salt formulation and the results support continued consideration as a potential medicine.
Ramot Y, Andreini I, Sacco G, Becker J, Bruhn K, Manno RA, Nyska A. Preclinical Safety Evaluation of BB106, a Novel Ketamine-Sulfobutylether-Beta-Cyclodextrin Salt, Following Subcutaneous Administration in Rats and Göttingen Minipigs. Int J Toxicol. 2026 Jan 20:10915818251414705. doi: 10.1177/10915818251414705.