title: Central nervous system penetration of oxycodone after intravenous and epidural administration.
abstract: BACKGROUND
  Despite being increasingly used for pain management, only two studies, with controversial results, have evaluated the epidural use of oxycodone.
  
  
  METHODS
  Twenty-four women, aged 26-64 yr, undergoing elective gynaecological surgery were enrolled in this randomized, double-blinded, parallel group study. The subjects were administered either i.v. oxycodone and epidural placebo (IV group; n=12) or epidural oxycodone and i.v. placebo (EPI group; n=12) after operation. Oxycodone was administered as a single dose of 0.1 mg kg(-1). An epidural catheter for drug administration was placed at T12/L1 and a spinal catheter for cerebrospinal fluid (CSF) sampling at L3/4. Plasma and CSF were frequently collected for the analysis of oxycodone and its major metabolites. The primary outcomes were the peak concentration (C(max)), time to peak concentration (T(max)), and the exposure (AUC(last)) of oxycodone in CSF and plasma. The secondary outcome was the analgesic efficacy, measured as the total dose of rescue fentanyl during the first four postoperative hours.
  
  
  RESULTS
  In the EPI group, the median oxycodone Cmax and AUC(last) in the CSF were 320- and 120-fold higher, respectively, compared with the IV group. The total dose of rescue fentanyl was significantly lower in the EPI group (seven subjects needed 16 doses) than in the IV group [12 subjects needed 71 doses (P=0.001)]. No serious or unexpected adverse events were reported.
  
  
  CONCLUSIONS
  Epidural oxycodone provides much higher CSF concentrations and possibly better analgesic efficacy than does i.v. oxycodone.
  
  
  BACKGROUND
  EudraCT reference number: 2011-000125-76.
authors.affiliation: Department of Anaesthesia and Operative Services and.
authors.forename: M
authors.initials: M
authors.lastname: Kokki
authors.forename: P
authors.initials: P
authors.lastname: Välitalo
authors.forename: M
authors.initials: M
authors.lastname: Kuusisto
authors.forename: V P
authors.initials: VP
authors.lastname: Ranta
authors.forename: K
authors.initials: K
authors.lastname: Raatikainen
authors.forename: H
authors.initials: H
authors.lastname: Hautajärvi
authors.forename: H
authors.initials: H
authors.lastname: Kokki
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001921:Brain / Q000378:metabolism*; D004311:Double-Blind Method; D004824:Epidural Space; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D010098:Oxycodone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D000701:Analgesics, Opioid; D010098:Oxycodone
keywords: administration, i.v.; analgesia, epidural, analgesics, opioid; oxycodone, pharmacokinetics