Single-Dose Pharmacokinetics of Fentanyl Buccal Soluble Film

Abstract

ObjectiveThe objectives of the study were to determine the absolute bioavailability of fentanyl from fentanyl buccal soluble film, estimate the percentage of a fentanyl dose absorbed through the buccal mucosa, and compare the bioavailability of equivalent doses administered either as single or multiple dose units.DesignOpen-label, randomized, four-period, Latin-square crossover pharmacokinetic study.SettingInpatient phase 1 unit.PatientsTwelve healthy volunteers.InterventionsInjectable fentanyl citrate (200 µg) administered by intravenous infusion, injectable fentanyl citrate (800 µg/16 mL) administered orally, and fentanyl buccal soluble film (800 µg) administered as a single film and as four separate 200 µg films simultaneously.Outcome MeasuresPlasma concentrations after fentanyl dosing; pharmacokinetic parameters.ResultsThe two buccal film treatments were bioequivalent and both had an absolute bioavailability of 71%. The percentage of an administered dose absorbed through the buccal mucosa was calculated to be 51%.ConclusionsFentanyl buccal soluble film effectively delivers a high percentage of the administered fentanyl dose and nearly identical plasma profiles are obtained when equivalent doses are delivered by single or multiple dosage units.

HPLC-UV method development for fentanyl determination in rat plasma and its application to elucidate pharmacokinetic behavior after i.p. administration to rats

“…administration is few. An IV administration of 200 μg FEN was conducted on humans, this study reported the pharmacokinetic parameters as follows; (C max ) of 1.46 ± 0.66 ng/mL, median (T max ) of 0.17 hours and (T 1/2 ) of 18.03 ± 10.08 hours [14]. This data shows a widely different change compared to rat, which can be ascribed to many factors; first: the different rout of administration and small blood volume of rat compared to human, second: amount of fatty tissue that enhance the distribution of FEN as it is considered to be highly lipophilic drug.…”

Efficacy and safety of fentanyl buccal for cancer pain management by administration through a soluble film: an update

“…The inactive layer isolates the bioadhesive layer from the buccal cavity, minimizing the amount of fentanyl that is swallowed and facilitating delivery directly to the buccal mucosa. [27][28][29] Once applied FBSF starts to dissolve in minutes and is completely dissolved within 15 to 30 minutes without patient effort. It requires a minimal quantity of saliva.…”

“…It has a BioErodible MucoAdhesive (BEMA ® ; BioDelivery Sciences, Inc., Raleigh, NC) delivery technology. 14,[27][28][29] This technology consists of two different layers made of water-soluble polymeric films, one bioadhesive layer and one inactive layer. The bioadhesive layer contains fentanyl citrate that adheres within seconds of making contact with the moist buccal mucosa.…”

“…It requires a minimal quantity of saliva. Delivered by this system, the proportion of the fentanyl dose that undergoes transmucosal absorption is approximately 50% and the absolute bioavailability is approximately 71% [29][30][31] (Table 1) …”

“…30 Consequently, the absorption surface area with a single 800-µg dose is exactly the same as with four individual 200-µg films. 29 Rauck et al in a multicenter, randomized, double-blind placebo-controlled, multiple-crossover study, with opioidtolerant adult patients with chronic cancer pain experiencing one to four daily episodes of breakthrough pain, showed that FBSF is an effective option for control of breakthrough pain in patients receiving ongoing opioid therapy.…”