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

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.

A Comprehensive Review of Rapid-Onset Opioids for Breakthrough Pain

“…[67] To date, the pharmacokinetics of INFS and SLF have been reported in patients with cancer and BTP; in these studies, INFS and SLF demonstrated pharmacokinetics that were comparable between patients and healthy volunteers. [57,58]…”

“…[58] Median t max values were between 12 and 15 minutes for INFS and the plasma concentration increased in a dose-dependent manner, although C max increased in a manner that was slightly less than proportional to the dose. Importantly, this study demonstrated that the pharmacokinetics of INFS in patients with cancer and BTP were comparable to previous results from studies in healthy volunteers.…”

“…Importantly, this study demonstrated that the pharmacokinetics of INFS in patients with cancer and BTP were comparable to previous results from studies in healthy volunteers. [58] In a study conducted in patients with pain after oral surgery, the bioavailability of INFS was 89% and t 1/2 was ∼6.5 minutes. [59]…”

Personalized Medicine for Classical Anesthesia Drugs and Cancer Progression

“…The measured and simulated plasma fentanyl concentrations increased, and increased adverse effects were seen from both subcutaneous and transdermal fentanyl [68]. A different study regarding the pharmacokinetics of intranasal fentanyl spray in patients with cancer was conducted to assess the tolerability and safety of this spray [69]. Neither of these studies measured the effect of the different formulations of fentanyl on cancer progression or the interaction with other drugs.…”

Fentanilo: una molécula y múltiples formulaciones galénicas de trascendencia clínica en el tratamiento del dolor irruptivo oncológico

“…En otro estudio de 19 pacientes oncológicos con dolor irruptivo, la Tmax osciló entre 12 y 15 minutos en dependencia de la dosis (50; 100 y 200 mcg). La concentración plasmática fue dosis dependiente, aunque el aumento de la Cmax (0,35 a 1,2 ng/ml) fue algo inferior a la proporcionalidad de la dosis (56). En los preparados de administración intranasal los niveles plasmáticos en sangre arterial parecen predecir mejor la acción farmacodinámica de fentanilo.…”