TY - JOUR
T1 - Prolongation of lidocaine-induced epidural anesthesia by medium molecular weight hyaluronic acid formulations
T2 - Pharmacodynamic and pharmacokinetic studies in the rabbit
AU - Doherty, M. M.
AU - Hughes, P. J.
AU - Korszniak, N. V.
AU - Charman, W. N.
PY - 1995/4/4
Y1 - 1995/4/4
N2 - We evaluated the utility of medium molecular weight hyaluronic acid for prolonging the local anesthetic activity of lidocaine in a rabbit model of epidural analgesia. Equiviscous formulations were prepared as either a physical mixture of lidocaine hydrochloride and sodium hyaluronate (where drug release occurred via diffusion) or as a lidocaine-hyaluronate complex (where drug release occurred via diffusional and electrostatic processes). The novel hyaluronic acid formulations were functionally evaluated, relative to lidocaine solution, in an intact, conscious 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 administration of the solution formulation, whereas only partial motor block was evident after administration of the viscous formulations. Pharmacokinetic modeling of the lidocaine plasma concentration- time data indicated that the rate of drug absorption from the lidocaine- hyaluronate complex was decreased fourfold relative to the solution (P < 0.05). These observations indicate that ionic complexes of local anesthetics with medium molecular weight hyaluronic acid may offer advantages for the prolongation of epidural analgesia.
AB - We evaluated the utility of medium molecular weight hyaluronic acid for prolonging the local anesthetic activity of lidocaine in a rabbit model of epidural analgesia. Equiviscous formulations were prepared as either a physical mixture of lidocaine hydrochloride and sodium hyaluronate (where drug release occurred via diffusion) or as a lidocaine-hyaluronate complex (where drug release occurred via diffusional and electrostatic processes). The novel hyaluronic acid formulations were functionally evaluated, relative to lidocaine solution, in an intact, conscious 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 administration of the solution formulation, whereas only partial motor block was evident after administration of the viscous formulations. Pharmacokinetic modeling of the lidocaine plasma concentration- time data indicated that the rate of drug absorption from the lidocaine- hyaluronate complex was decreased fourfold relative to the solution (P < 0.05). These observations indicate that ionic complexes of local anesthetics with medium molecular weight hyaluronic acid may offer advantages for the prolongation of epidural analgesia.
UR - http://www.scopus.com/inward/record.url?scp=0028920468&partnerID=8YFLogxK
U2 - 10.1097/00000539-199504000-00016
DO - 10.1097/00000539-199504000-00016
M3 - Article
C2 - 7893028
AN - SCOPUS:0028920468
SN - 0003-2999
VL - 80
SP - 740
EP - 746
JO - Anesthesia and Analgesia
JF - Anesthesia and Analgesia
IS - 4
ER -