title: Epidural, intrathecal pharmacokinetics, and intrathecal bioavailability of ropivacaine.
abstract: BACKGROUND
  Ropivacaine is used by the epidural route for postoperative pain management with various neuraxial techniques. Given the widespread use of these techniques and the relative paucity of data on spinal disposition of local anesthetics, we evaluated through an experimental animal model, the spinal disposition of ropivacaine, allowing further studies of factors influencing their intrathecal bioavailability.
  
  
  METHODS
  Sheep received an IV bolus dose of ropivacaine (50 mg), and 1 wk after, an intrathecal dose of ropivacaine (20 mg) followed 3 h later by epidural ropivacaine (100 mg). A simultaneous microdialysis technique was used to measure epidural and intrathecal drug concentrations after both epidural and intrathecal administrations.
  
  
  RESULTS
  Absorption-time plots showed a large variability in the systemic absorption after both intrathecal and epidural administration, with an apparent faster systemic absorption after intrathecal administration. In the intrathecal space, the elimination clearance was around three-times higher than the distribution clearance. In the epidural space, the relative contribution of elimination and distribution to ropivacaine disposition was different, indicating a more pronounced influence of the distribution process. The intrathecal bioavailability after epidural administration was 11.1% +/- 7.6%.
  
  
  CONCLUSIONS
  Using an animal model, we showed that drug dispositions in the intrathecal and epidural compartments are different, and that the intrathecal bioavailability of ropivacaine after epidural administration is low, and highly variable.
authors: Laboratoire de Pharmacie Galénique, Biopharmacie et Pharmacie Clinique, Université de Rennes 1, Rennes Cedex, France.
authors: François-Xavier
authors: FX
authors: Rose
authors: Jean-Pierre
authors: JP
authors: Estebe
authors: Maja
authors: M
authors: Ratajczak
authors: Eric
authors: E
authors: Wodey
authors: François
authors: F
authors: Chevanne
authors: Gilles
authors: G
authors: Dollo
authors: David
authors: D
authors: Bec
authors: Jean-Marc
authors: JM
authors: Malinovsky
authors: Claude
authors: C
authors: Ecoffey
authors: Pascal
authors: P
authors: Le Corre
mesh_terms: D000577:Amides / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D004824:Epidural Space / Q000378:metabolism; D005260:Female; D007268:Injections, Epidural; D007275:Injections, Intravenous; D007278:Injections, Spinal; D017551:Microdialysis; D023421:Models, Animal; D008954:Models, Biological; D000077212:Ropivacaine; D012756:Sheep; D013116:Spinal Cord / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine