Effects of smoking and body mass index on the exposure of fentanyl in patients with cancer

Evelien Kuip; Wendy Oldenmenger; Martine Visser; Peter de Bruijn; Astrid Oosten; Esther Oomen - de Hoop; Stijn Koolen; Karin van der Rijt; Ron Mathijssen

doi:10.1371/journal.pone.0198289

Effects of smoking and body mass index on the exposure of fentanyl in patients with cancer

Evelien Kuip^*, Wendy Oldenmenger, Martine Visser, Peter de Bruijn, Astrid Oosten, Esther Oomen - de Hoop, Stijn Koolen, Karin van der Rijt, Ron Mathijssen

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

The transdermal fentanyl patch is widely used to treat cancer-related pain despite its wide inter- and intrapatient variability in pharmacokinetics. The aim of this study was to investigate whether smoking and body size (i.e. body mass index) influence fentanyl exposure in patients with cancer. These are factors that typically change during treatment and disease trajectories. We performed an explorative cohort study in patients with cancer using transdermal fentanyl patches (Durogesic^®), by taking a blood sample for pharmacokinetic analysis one day after applying a patch in patients with a stable fentanyl dose. A total of 88 patients were evaluable. Although no statistically significant difference was found, the plasma concentrations of non-smokers was 28% (95% CI [-14%; +89-%]) higher than those of smokers normalizing for a dose of 25μg/min. Patients with a low BMI (< 20 kg/m2) had almost similar (10% (95% CI [-39%; +97%]) higher) plasma concentrations compared to patients with a high BMI (> 25 kg/m2). A wider variation in fentanyl plasma concentrations was found in this study than anticipated. Due to this variation, studies in larger patient cohorts are needed to further investigate the effect of smoking on plasma concentration of fentanyl and thereby clarify the clinical significance of our findings.

Original language	English
Article number	e0198289
Journal	PLoS One (online)
Volume	13
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0198289
Publication status	Published - 8 Jun 2018

Bibliographical note

Publisher Copyright:
© 2018 Kuip et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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title = "Effects of smoking and body mass index on the exposure of fentanyl in patients with cancer",

abstract = "The transdermal fentanyl patch is widely used to treat cancer-related pain despite its wide inter- and intrapatient variability in pharmacokinetics. The aim of this study was to investigate whether smoking and body size (i.e. body mass index) influence fentanyl exposure in patients with cancer. These are factors that typically change during treatment and disease trajectories. We performed an explorative cohort study in patients with cancer using transdermal fentanyl patches (Durogesic{\textregistered}), by taking a blood sample for pharmacokinetic analysis one day after applying a patch in patients with a stable fentanyl dose. A total of 88 patients were evaluable. Although no statistically significant difference was found, the plasma concentrations of non-smokers was 28% (95% CI [-14%; +89-%]) higher than those of smokers normalizing for a dose of 25μg/min. Patients with a low BMI (< 20 kg/m2) had almost similar (10% (95% CI [-39%; +97%]) higher) plasma concentrations compared to patients with a high BMI (> 25 kg/m2). A wider variation in fentanyl plasma concentrations was found in this study than anticipated. Due to this variation, studies in larger patient cohorts are needed to further investigate the effect of smoking on plasma concentration of fentanyl and thereby clarify the clinical significance of our findings.",

author = "Evelien Kuip and Wendy Oldenmenger and Martine Visser and {de Bruijn}, Peter and Astrid Oosten and {Oomen - de Hoop}, Esther and Stijn Koolen and {van der Rijt}, Karin and Ron Mathijssen",

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AU - Oosten, Astrid

AU - Oomen - de Hoop, Esther

AU - Koolen, Stijn

AU - van der Rijt, Karin

AU - Mathijssen, Ron

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N2 - The transdermal fentanyl patch is widely used to treat cancer-related pain despite its wide inter- and intrapatient variability in pharmacokinetics. The aim of this study was to investigate whether smoking and body size (i.e. body mass index) influence fentanyl exposure in patients with cancer. These are factors that typically change during treatment and disease trajectories. We performed an explorative cohort study in patients with cancer using transdermal fentanyl patches (Durogesic®), by taking a blood sample for pharmacokinetic analysis one day after applying a patch in patients with a stable fentanyl dose. A total of 88 patients were evaluable. Although no statistically significant difference was found, the plasma concentrations of non-smokers was 28% (95% CI [-14%; +89-%]) higher than those of smokers normalizing for a dose of 25μg/min. Patients with a low BMI (< 20 kg/m2) had almost similar (10% (95% CI [-39%; +97%]) higher) plasma concentrations compared to patients with a high BMI (> 25 kg/m2). A wider variation in fentanyl plasma concentrations was found in this study than anticipated. Due to this variation, studies in larger patient cohorts are needed to further investigate the effect of smoking on plasma concentration of fentanyl and thereby clarify the clinical significance of our findings.

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Effects of smoking and body mass index on the exposure of fentanyl in patients with cancer

Abstract

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