COMPARATIVE LOCAL-ANESTHETIC EFFICACY AND PHARMACOKINETICS OF EPIDURALLY ADMINISTERED ROPIVACAINE AND BUPIVACAINE IN THE SHEEP

Background and Objectives. Ropivacaine is the S(-) propyl homolog of b upivacaine and mepivacaine. Studies in humans have confirmed the resul ts of studies in laboratory animals that ropivacaine is a long-acting local anesthetic with an anesthetic profile similar to bupivacaine. Ac ute, intravenous systemic toxicity studies have been conducted in shee p and dogs. Local anesthetic efficacy has been studied after epidural administration in the dog. This study was initiated to determine the l ocal anesthetic efficacy and pharmacokinetics of ropivacaine and bupiv acaine after epidural administration in an experimental sheep model an d to evaluate the sheep model as a model of experimental epidural anes thesia. Methods. Twelve adult nonpregnant ewes were prepared with chro nically implanted lumbar epidural catheters and arterial lines. Each s heep received injections of 5.0 mL ropivacaine and bupivacaine (0.5% a nd 0.75%) in a blinded, random, cross-over fashion. Onset and duration of sensory and motor blockade were evaluated. Arterial blood samples were drawn for serum drug concentration determinations and pharmacokin etic analysis. Results. Onset and duration of motor blockade were simi lar for comparable concentrations of both drugs. Both concentrations o f ropivacaine and bupivacaine 0.5% demonstrated differential neural bl ockade. The peak serum concentrations generally occurred within 8 minu tes after administration. The terminal elimination half-life in serum was about 3.5-4.0 hours and 6 hours for ropivacaine and bupivacaine, r espectively. No signs of systemic toxicity were observed. Results of s ensory and motor blockade were consistent with previous studies in lab oratory animals and humans. Conclusion. Ropivacaine produces sensory a nd motor blockade which is similar to that produced by equal concentra tions of bupivacaine after epidural administration in the sheep. Peak serum concentrations produced no signs of systemic toxicity. The resul ts of this study are consistent with previously published data from st udies in laboratory animals and humans. The sheep model of experimenta l epidural anesthesia appears to be a clinically relevant method to ev aluate experimental local anesthetics.