title: Pharmacokinetics of levobupivacaine, fentanyl, and clonidine after administration in thoracic paravertebral analgesia.
abstract: OBJECTIVE
  There is little knowledge of the pharmacokinetics of local anesthetics and adjunctive analgesics after paravertebral blockade. We evaluated the pharmacokinetics of low-dose levobupivacaine, fentanyl, and clonidine after paravertebral analgesia for breast surgery.
  
  
  METHODS
  Thirty-eight patients receiving paravertebral analgesia for breast surgery received a 19-mL paravertebral bolus of levobupivacaine 0.25% combined with a 1-mL volume of saline (group L, 13 patients), fentanyl 50 microg (group LF, 13 patients), or clonidine 150 microg (group LC, 12 patients) followed 1 hour later by infusion of levobupivacaine 0.1% (L), levobupivacaine 0.05% with fentany l 4 microg/mL (LF), or levobupivacaine 0.05% with clonidine 3 microg/mL (LC), respectively. Plasma concentrations of study drugs were determined at intervals up to 24 hours after bolus injection.
  
  
  RESULTS
  There was rapid absorption of levobupivacaine after bolus with mean (standard deviation) maximum plasma concentration (Cpmax) of 0.51(0.24) microg/mL in a median time to maximum concentration tCpmax of 15 minutes. Mean Cpmax fentanyl and clonidine after bolus were 0.62 (0.37) and 0.79 (0.23) ng/mL, in a median tCpmax of 15 and 22.5 minutes, respectively. Mean Cpmax levobupivacaine after infusion was 0.47 (0.41) microg/mL in a median tCpmax of 24 hours. There was progressive accumulation of fentanyl and clonidine at 24 hours with a mean Cpmax of 0.72 (0.33) and 1.74 (0.70) ng/mL, respectively.
  
  
  CONCLUSIONS
  After paravertebral bolus and infusion administration, Cpmax levobupivacaine was within the safe range. Cpmax fentanyl and clonidine were less than the effective levels after IV administration, suggesting that their analgesic effect may be partly attributed to a peripheral mechanism of action.
authors.affiliation: Department of Anaesthesia, Intensive Care and Pain Medicine, Mater Misericordiae University Hospital, Dublin, Ireland. crina@ireland.com
authors.forename: Crina L
authors.initials: CL
authors.lastname: Burlacu
authors.forename: Henry P
authors.initials: HP
authors.lastname: Frizelle
authors.forename: Denis C
authors.initials: DC
authors.lastname: Moriarty
authors.forename: Donal J
authors.initials: DJ
authors.lastname: Buggy
mesh_terms: D000328:Adult; D000698:Analgesia; D000779:Anesthetics, Local / Q000097:blood / Q000493:pharmacokinetics*; D001943:Breast Neoplasms / Q000601:surgery; D002045:Bupivacaine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D003000:Clonidine / Q000097:blood / Q000493:pharmacokinetics*; D004333:Drug Administration Routes; D005260:Female; D005283:Fentanyl / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D000077554:Levobupivacaine; D013058:Mass Spectrometry; D008875:Middle Aged; D010149:Postoperative Pain / Q000517:prevention & control; D013904:Thoracic Vertebrae / Q000294:innervation
chemical_list: D000779:Anesthetics, Local; D000077554:Levobupivacaine; D003000:Clonidine; D005283:Fentanyl; D002045:Bupivacaine