Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic of CZ1S Injection for Unilateral Brachial Plexus Blockade in Healthy Chinese Adults: Double-blind, Randomized, Positive-controlled Phase I Study

CZ1S injection is a novel, extended-release local anaesthetic formulation of ropivacaine, classified as a type 2.2 new drug, with potential for post-operative analgesia by subcutaneous infiltration and peripheral nerve blockade. This study aimed to validate the superior properties of CZ1S over ropivacaine hydrochloride injection and to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of a single dose of brachial plexus block with CZ1S in healthy Chinese adults. The tolerability and PK profile of CZ1S were investigated following a unilateral brachial plexus injection in 24 healthy adults. Safety assessments were performed throughout the study and the PD effects of CZ1S injection for unilateral brachial plexus block were also evaluated. The results showed that CZ1S was slowly absorbed after a single injection in healthy subjects, with PK parameters of ropivacaine (including C_max, AUC_t and AUC_∞) increasing with the CZ1S doses. CZ1S demonstrated a prolonged and non-constant release profile compared to a single 75 mg injection of ropivacaine hydrochloride, resulting in a smooth and sustained blood concentration. CZ1S significantly prolonged the duration of sensory and motor blockade, and further analysis revealed a correlation between PK and sensory nerve blocks. The PK profile of CZ1S was enhanced compared to that of ropivacaine injection, and it was deemed safe and well tolerated in healthy Chinese adults, suggesting its potential application in postoperative analgesia.