title: Prior epidural lidocaine alters the pharmacokinetics and drug effects of extended-release epidural morphine (DepoDur®) after cesarean delivery.
abstract: BACKGROUND
  A potential physicochemical interaction between epidural local anesthetics and extended-release epidural morphine (EREM) could negate the sustained release. In this study, we sought to determine the pharmacokinetic and drug effects of prior epidural lidocaine administration on EREM.
  
  
  METHODS
  Thirty healthy women undergoing cesarean delivery were enrolled in this randomized study. Patients received 8 mg EREM 1 hour after either a combined spinal-epidural (intrathecal bupivacaine and fentanyl 20 μg with no epidural medication; group SE) or an epidural anesthetic (epidural 2% lidocaine with fentanyl 100 μg; group E). Maximal concentration (Cmax), time to Cmax (Tmax), and AUC(0-last) (area under the concentration-time curve until the last plasma concentration that was below the limit of quantitation) for morphine levels were determined from a plasma sample at 0, 5, 10, 15, and 30 minutes, and 1, 4, 8, 12, 24, 36, 48, and 72 hours. Drug effects including pain, analgesic use, and side effects were measured for 72 hours after cesarean delivery.
  
  
  RESULTS
  Epidural lidocaine administration (20-35 mL) 1 hour before epidural EREM administration increased the Cmax in group E (11.1 ± 4.9) compared with group SE (8.3 ± 7.1 ng/mL) (P = 0.038). There were no significant effects on Tmax and AUC(0-last) of venous morphine between the groups (P > 0.05). There was an increased incidence in vomiting, oxygen use, and hypotension in group E (patients who received lidocaine before EREM).
  
  
  CONCLUSIONS
  A large dose of epidural lidocaine 1 hour before EREM administration alters the pharmacokinetics and drug effects of EREM. Clinicians must apply caution when EREM is administered even 1 hour after an epidural lidocaine "top-up" for cesarean delivery.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Atkinson Ralls
authors.forename: David R
authors.initials: DR
authors.lastname: Drover
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Clavijo
authors.forename: Brendan
authors.initials: B
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000767:Anesthesia, Epidural; D000773:Anesthesia, Obstetrical; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D002585:Cesarean Section; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology*; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D010149:Postoperative Pain / Q000188:drug therapy*; D020250:Postoperative Nausea and Vomiting / Q000453:epidemiology; D011247:Pregnancy
chemical_list: D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D009020:Morphine; D008012:Lidocaine