title: The Cerebrospinal Fluid Distribution of Postoperatively Administred Dexketoprofen and Etoricoxib and Their Effect on Pain and Inflammatory Markers in Patients Undergoing Hip Arthroplasty.
abstract: OBJECTIVE
  Based on earlier literature, etoricoxib may have a delayed analgesic effect in postoperative setting when analgesic efficacy of nonselective nonsteroidal anti-inflammatory drug dexketoprofen is rapid. This may be caused by slow penetration of etoricoxib into the central nervous system (CNS). Therefore we decided to determine the plasma and cerebrospinal fluid (CSF) pharmacokinetics and pharmacodynamics of dexketoprofen and etoricoxib in patients with hip arthroplasty.
  
  
  METHODS
  A total of 24 patients, scheduled for an elective primary hip arthroplasty were enrolled. After surgery, 12 subjects were randomized to received a single intravenous dose of dexketoprofen, and 12 subjects were given oral etoricoxib. Paired blood and CSF samples were taken up to 24 h for measurement of drug concentrations, interleukin (IL)-6, IL-1ra and blood for interleukin 10.
  
  
  RESULTS
  In CSF the highest measured concentration (C max) of dexketoprofen was 4.0 (median) ng/mL (minimum-maximum 1.9-13.9) and time to the highest concentration (t max) 3 h (2-5), and for etoricoxib C max 73 ng/mL (36-127) and t max 5 h (1-24), respectively. Opioid consumption during the first 24 postoperative hours was similar in the two groups. Dexketoprofen and etoricoxib had a similar effect on the postoperative inflammatory response. No significant differences considering pain relief or adverse events were found between the two groups.
  
  
  CONCLUSIONS
  Dexketoprofen and etoricoxib entered the CNS readily, already at 30 min after administration dexketoprofen was detected in the CSF in most subjects and etoricoxib after 60 min. A single dose of dexketoprofen and etoricoxib provided a similar anti-inflammatory and analgesic response after major orthopaedic surgery.
authors.affiliation: Department of Anaesthesia and Operative Services, Kuopio University Hospital, PO Box 100, 70029, Kuopio, Finland.|Department of Anaesthesiology and Intensive Care, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Annika
authors.initials: A
authors.lastname: Piirainen
authors.affiliation: Department of Anaesthesia and Operative Services, Kuopio University Hospital, PO Box 100, 70029, Kuopio, Finland. merja.kokki@kuh.fi.|Department of Anaesthesiology and Intensive Care, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland. merja.kokki@kuh.fi.
authors.forename: Merja
authors.initials: M
authors.lastname: Kokki
authors.affiliation: Admescope Ltd, Oulu, Finland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Hautajärvi
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Lehtonen
authors.affiliation: Department of Orthopaedic Surgery, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Miettinen
authors.affiliation: Department of Clinical Chemistry University of Eastern Finland, Eastern Finland Laboratory Centre Joint Authority Enterprise (ISLAB), Kuopio, Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Pulkki
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Veli-Pekka
authors.initials: VP
authors.lastname: Ranta
authors.affiliation: Department of Anaesthesia and Operative Services, Kuopio University Hospital, PO Box 100, 70029, Kuopio, Finland.|Department of Anaesthesiology and Intensive Care, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Kokki
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019644:Arthroplasty, Replacement, Hip; D016207:Cytokines / Q000097:blood*; D000077613:Etoricoxib; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007660:Ketoprofen / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control*; D017060:Patient Satisfaction; D011446:Prospective Studies; D011725:Pyridines / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013450:Sulfones / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; C508609:IL10 protein, human; C508600:IL6 protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D011725:Pyridines; D013450:Sulfones; D016753:Interleukin-10; D007660:Ketoprofen; D000077613:Etoricoxib