title: Saliva versus Plasma for Pharmacokinetic and Pharmacodynamic Studies of Fentanyl in Patients with Cancer.
abstract: OBJECTIVE
  Fentanyl is widely used to relieve cancer pain. However there is great interpatient variation in the dose required to relieve pain and little knowledge about the pharmacokinetic and pharmacodynamic (PK/PD) relationship of fentanyl and pain control. Patients with cancer are fragile and there is reluctance on the part of health professionals to take multiple plasma samples for PK/PD studies. The relationship between plasma and saliva fentanyl concentrations was investigated to determine whether saliva could be a valid substitute for plasma in PK/PD studies.
  
  
  METHODS
  One hundred sixty-three paired plasma and saliva samples were collected from 56 patients prescribed transdermal fentanyl (Durogesic, Janssen-Cilag Pty Limited, NSW, Australia) at varying doses (12-200 µg/h). Pain scores were recorded at the time of sampling. Fentanyl and norfentanyl concentrations in plasma and saliva were quantified using HPLC-MS/MS.
  
  
  RESULTS
  Saliva concentrations of fentanyl (mean = 4.84 μg/L) were much higher than paired plasma concentrations of fentanyl (mean = 0.877 μg/L). Both plasma and saliva mean concentrations of fentanyl were well correlated with dose with considerable interpatient variation at each dose. The relationship between fentanyl and norfentanyl concentrations was poor in both plasma and saliva. No correlation was observed between fentanyl concentration in plasma and saliva (r(2) = 0.3743) or free fentanyl in plasma and total saliva concentrations (r(2) = 0.1374). Pain scores and fentanyl concentration in either of the matrices were also not correlated.
  
  
  CONCLUSIONS
  No predictive correlation was observed between plasma and saliva fentanyl concentration. However the detection of higher fentanyl concentrations in saliva than plasma, with a good correlation to dose, may allow saliva to be used as an alternative to plasma in PK/PD studies of fentanyl in patients with cancer.
authors.affiliation: School of Pharmacy, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia. Electronic address: s.bista@griffith.edu.au.
authors.forename: Sudeep R
authors.initials: SR
authors.lastname: Bista
authors.affiliation: School of Pharmacy, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia; Mater Research Institute, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Alison
authors.initials: A
authors.lastname: Haywood
authors.affiliation: School of Pharmacy, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia; Mater Research Institute, The University of Queensland, Brisbane, Queensland, Australia; SydPath, St Vincent's Hospital, Sydney, New South Wales, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: Norris
authors.affiliation: Mater Research Institute, The University of Queensland, Brisbane, Queensland, Australia; Department of Palliative and Supportive Care, Mater Health Services, Brisbane, Queensland, Australia; Palliative Care, St Vincent's Private Hospital, Brisbane, Queensland, Australia.
authors.forename: Phillip
authors.initials: P
authors.lastname: Good
authors.affiliation: Department of Palliative and Supportive Care, Mater Health Services, Brisbane, Queensland, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Tapuni
authors.affiliation: Mater Pathology Services, South Brisbane, Queensland, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Lobb
authors.affiliation: Mater Research Institute, The University of Queensland, Brisbane, Queensland, Australia; Department of Palliative and Supportive Care, Mater Health Services, Brisbane, Queensland, Australia.
authors.forename: Janet
authors.initials: J
authors.lastname: Hardy
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D012463:Saliva / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000701:Analgesics, Opioid; C080127:norfentanyl; D005283:Fentanyl
keywords: cancer pain; fentanyl; opioid; pharmacokinetics; plasma; saliva