Saliva versus plasma for pharmacokinetic and pharmacodynamic studies of fentanyl in patients with cancer

Bista, Sudeep R., Haywood, Alison, Norris, Ross, Good, Phillip, Tapuni, Angela, Lobb, Michael and Hardy, Janet (2015) Saliva versus plasma for pharmacokinetic and pharmacodynamic studies of fentanyl in patients with cancer. Clinical Therapeutics, 37 11: 2468-2475. doi:10.1016/j.clinthera.2015.09.002

Author Bista, Sudeep R.
Haywood, Alison
Norris, Ross
Good, Phillip
Tapuni, Angela
Lobb, Michael
Hardy, Janet
Title Saliva versus plasma for pharmacokinetic and pharmacodynamic studies of fentanyl in patients with cancer
Journal name Clinical Therapeutics   Check publisher's open access policy
ISSN 1879-114X
Publication date 2015-11-01
Sub-type Article (original research)
DOI 10.1016/j.clinthera.2015.09.002
Open Access Status Not Open Access
Volume 37
Issue 11
Start page 2468
End page 2475
Total pages 8
Place of publication New York, NY, United States
Publisher Elsevier
Collection year 2016
Language eng
Formatted abstract
Purpose: 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.

Findings: 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 (r2 = 0.3743) or free fentanyl in plasma and total saliva concentrations (r2 = 0.1374). Pain scores and fentanyl concentration in either of the matrices were also not correlated.

Implications: 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.
Keyword Fentanyl
Cancer pain
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
School of Agriculture and Food Sciences
Official 2016 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 3 times in Thomson Reuters Web of Science Article | Citations
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