Objective: This study reports the pharmacokinetics, tolerability, and safety of an intranasalfentanyl 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 microg. 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 T(max) values were 15, 12, and 15 minutes for the 50, 100, and 200 microg doses of INFS, respectively. Mean (SD) values for C(max) 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 microg showed a short T(max) and was well tolerated in patients with cancer. These results support INFS use in patients with cancer suffering from BTP.