title: Comparative local anesthetic efficacy and pharmacokinetics of epidurally administered ropivacaine and bupivacaine in the sheep.
abstract: OBJECTIVE
  Ropivacaine is the S(-) propyl homolog of bupivacaine and mepivacaine. Studies in humans have confirmed the results of studies in laboratory animals that ropivacaine is a long-acting local anesthetic with an anesthetic profile similar to bupivacaine. Acute, intravenous systemic toxicity studies have been conducted in sheep and dogs. Local anesthetic efficacy has been studied after epidural administration in the dog. This study was initiated to determine the local anesthetic efficacy and pharmacokinetics of ropivacaine and bupivacaine after epidural administration in an experimental sheep model and to evaluate the sheep model as a model of experimental epidural anesthesia.
  
  
  METHODS
  Twelve adult nonpregnant ewes were prepared with chronically implanted lumbar epidural catheters and arterial lines. Each sheep received injections of 5.0 mL ropivacaine and bupivacaine (0.5% and 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 pharmacokinetic analysis.
  
  
  RESULTS
  Onset and duration of motor blockade were similar for comparable concentrations of both drugs. Both concentrations of ropivacaine and bupivacaine 0.5% demonstrated differential neural blockade. The peak serum concentrations generally occurred within 8 minutes after administration. The terminal elimination half-life in serum was about 3.5-4.0 hours and 6 hours for ropivacaine and bupivacaine, respectively. No signs of systemic toxicity were observed. Results of sensory and motor blockade were consistent with previous studies in laboratory animals and humans.
  
  
  CONCLUSIONS
  Ropivacaine produces sensory and motor blockade which is similar to that produced by equal concentrations of bupivacaine after epidural administration in the sheep. Peak serum concentrations produced no signs of systemic toxicity. The results of this study are consistent with previously published data from studies in laboratory animals and humans. The sheep model of experimental epidural anesthesia appears to be a clinically relevant method to evaluate experimental local anesthetics.
authors.affiliation: Department of Anesthesia Research Laboratories, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Feldman
authors.forename: S
authors.initials: S
authors.lastname: Dvoskin
authors.forename: M H
authors.initials: MH
authors.lastname: Halldin
authors.forename: A L
authors.initials: AL
authors.lastname: Ask
authors.forename: A M
authors.initials: AM
authors.lastname: Doucette
mesh_terms: D000577:Amides / Q000009:adverse effects / Q000493:pharmacokinetics; D000767:Anesthesia, Epidural / Q000009:adverse effects; D000779:Anesthetics, Local / Q000009:adverse effects / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D002045:Bupivacaine / Q000009:adverse effects / Q000493:pharmacokinetics; D002404:Catheterization; D005260:Female; D006207:Half-Life; D009046:Motor Neurons / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D000077212:Ropivacaine; D012756:Sheep
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D002045:Bupivacaine