D3.323 - SBK007: A Novel Oral H1 Antihistamine with Rapid Onset (30min): Preclinical Pharmacodynamics in Acute Urticaria

The primary goal of acute urticaria (AU) initial treatment is rapid relief of pruritus and wheals. While second-generation oral H1 antihistamines are clinically used, their slow onset fails to meet "immediate symptom control" needs in emergency/severe cases, leaving a global unmet demand for fast-acting oral regimens. SBK007, a novel oral H1 antihistamine developed by our company, shows rapid onset and potent efficacy in preclinical studies, promising quicker AU symptom relief. 

To systematically evaluate SBK007’s effects on key pathological processes of AU using three classic in vivo models, clarify its advantages in efficacy and onset speed, and provide experimental evidence for clinical translation.

All animals (male/female equally) were randomly grouped, dosed via gavage, with ebastine as positive control. Key groups and endpoints: 

Model 1: Rat Cutaneous Vascular Permeability 

-Animals: 60 SD rats 

-Groups: Model + SBK007 (0.01/0.02/0.04 mmol/kg) + Ebastine (0.01/0.02 mmol/kg) 

-Treatment: Post-dosing, histamine + Evans blue were injected. Back spot area measured at 30/60/90/120 min; inhibition rate calculated. 

Model 2: Mouse Pruritus 

-Animals: 84 ICR mice 

-Groups: Normal + Model + SBK007 (0.014/0.028/0.056 mmol/kg) + Ebastine (0.014/0.028 mmol/kg) 

-Treatment: Post-dosing, 4-aminopyridine injected. Pruritus latency and licking times within 10 min recorded. 

Model 3: Guinea Pig Asthma 

-Animals: 60 guinea pigs 

-Groups: Model + SBK007 (0.0087/0.0174/0.0348 mmol/kg) + Ebastine (0.0087/0.0174 mmol/kg) 

-Treatment: Post-dosing, histamine nebulized. Asthma onset latency observed. 

SBK007 exhibited significant inhibitory effects in all three models with a clear dose-effect relationship (P<0.001 vs. model group). At equimolar doses, its efficacy and onset speed were significantly superior to ebastine (see Tables 1-3).  

Preliminary in vitro metabolic data show SBK007 exerts pharmacological effects directly without hepatic metabolism, enabling peak efficacy within 30 min post-dosing—precisely addressing emergency AU patients’ "immediate symptom control" need. Its potent inhibition may reduce clinical dosage and enhance safety. Compared with existing therapies, SBK007 offers a more convenient, effective oral option for AU patients (especially severe/emergency cases) and holds substantial clinical translation potential.