PROLONGATION OF LIDOCAINE-INDUCED EPIDURAL-ANESTHESIA BY MEDIUM MOLECULAR-WEIGHT HYALURONIC-ACID FORMULATIONS - PHARMACODYNAMIC AND PHARMACOKINETIC STUDIES IN THE RABBIT

We evaluated the utility of medium molecular weight hyaluronic acid fo r prolonging the local anesthetic activity of lidocaine in a rabbit mo del of epidural analgesia. Equiviscous formulations were prepared as e ither a physical mixture of lidocaine hydrochloride and sodium hyaluro nate (where drug release occurred via diffusion) or as a lidocaine-hya luronate complex (where drug release occurred via diffusional and elec trostatic processes). The novel hyaluronic acid formulations were func tionally evaluated, relative to lidocaine solution, in an intact, cons cious rabbit model. The hyaluronate formulations were well tolerated. The duration of sensory block and loss of weight-bearing was prolonged twofold by the lidocaine-hyaluronate complex relative to the solution (P < 0.05). In terms of motor block, flaccid paresis occurred after a dministration of the solution formulation, whereas only partial motor block was evident after administration of the viscous formulations. Ph armacokinetic modeling of the lidocaine plasma concentration-time data indicated that the rate of drug absorption from the lidocaine-hyaluro nate complex was decreased fourfold relative to the solution (P < 0.05 ). These observations indicate that ionic complexes of local anestheti cs with medium molecular weight hyaluronic acid may offer advantages f or the prolongation of epidural analgesia.