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.
Key words
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Article info
Publication history
Published online: September 21, 2015
Accepted:
September 1,
2015
Identification
Copyright
© 2015 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
