Pharmacokinetics of intranasal fentanyl spray in patients with cancer and breakthrough pain

Stein Kaasa, MD, PhD; Kristin Moksnes, MD; Thomas Nolte, MD; Daniele Lefebvre-Kuntz, MD; Lars Popper, MS, PhD; Hans Georg Kress, MD, PhD

doi:10.5055/jom.2010.0001

Authors

Stein Kaasa, MD, PhD
Kristin Moksnes, MD
Thomas Nolte, MD
Daniele Lefebvre-Kuntz, MD
Lars Popper, MS, PhD
Hans Georg Kress, MD, PhD

DOI:

https://doi.org/10.5055/jom.2010.0001

Keywords:

intranasal administration, fentanyl, pharmacokinetics

Abstract

Objective: This study reports the pharmacokinetics, tolerability, and safety of an intranasal fentanyl spray (INFS) in patients with cancer and breakthrough pain (BTP).
Design: A randomized, open-label, two-period, crossover trial.
Patients: Nineteen adult patients (mean 57.8 years) with BTP, receiving opioid treatment for chronic background pain, from clinical departments in Austria, France, and Norway entered and completed the study.
Intervention: Patients were randomly assigned to receive one of six INFS dose sequences: 50/100, 100/50, 50/200, 200/50, 100/200, and 200/100 μg. INFS was administered as a single dose in one nostril. Each dose was separated by a minimum of 48 hours.
Main outcome measure: Plasma fentanyl concentrations were measured by high-performance liquid chromatography and tandem mass spectrometry from blood samples obtained at 0 (predose) and frequently up to 300 minutes after INFS administration. Blood pressure, peripheral oxygen saturation, and respiratory rate were assessed eight times during each of the two treatment periods.
Results: Mean fentanyl plasma concentrations increased in a dose-dependent manner, peaking for all fentanyl doses 9-15 minutes after INFS administration. Median Tmax values were 15, 12, and 15 minutes for the 50, 100, and 200 μg doses of INFS, respectively. Mean (SD) values for Cmax were 351 (±226), 595 (±400), and 1195 (±700) pg/mL, respectively, indicating dose-proportionality. Six patients (31.6 percent) experienced adverse events during the treatment period, the majority being mild in severity.
Conclusion: INFS at doses of 50, 100, and 200 μg showed a short Tmax and was well tolerated in patients with cancer. These results support INFS use in patients with cancer suffering from BTP.

Author Biographies

Stein Kaasa, MD, PhD

Pain and Palliation Research Group, Department of Cancer Research and Molecular Medicine, Medical Faculty, Norwegian University of Science and Technology and Palliative Medicine Unit, Trondheim University Hospital, Trondheim, Norway.

Kristin Moksnes, MD

Pain and Palliation Research Group, Department of Circulation and Medical Imaging, Medical Faculty, Norwegian University of Science and Technology, Trondheim, Norway.

Thomas Nolte, MD

Centre for Pain Therapy and Palliative Care, Medical Specialist Centre, Wiesbaden, Germany.

Daniele Lefebvre-Kuntz, MD

Centre Oscar Lambret, Anesthesiology, Resuscitaion & Pain Services, 3, rue F. Combemale, Lille, France.

Lars Popper, MS, PhD

Research and Development, Nycomed, Langebjerg, Roskilde, Denmark.

Hans Georg Kress, MD, PhD

Medical University/AKH Vienna, Department of Special Anaesthesia and Pain Therapy, Waehringer Guertel 18-20, Vienna, Austria.

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