A Phase I Pharmacokinetic and Bioavailability Study of a Sublingual Fentanyl Wafer in Healthy Volunteers

BACKGROUND: The sublingual administration of opioids is a simple and noninvasive method that provides rapid analgesia. In this phase I study we investigated the pharmacokinetics and bioavailability of a fentanyl wafer in healthy volunteers. The principal study objective was to investigate the pharmacokinetic profile of a new sublingual fentanyl wafer and to establish its absolute bioavailability. METHODS: Twenty-four healthy volunteers, mean age 23 years, were randomly assigned to receive the equivalent of fentanyl 100 mu g by both the sublingual and IV routes. Blood samples were collected in sterile polypropylene tubes for 24 hours after each fentanyl administration. The pharmacokinetic parameters were determined by model-independent pharmacokinetic analyses of the plasma fentanyl concentration-time profiles. RESULTS: The mean absolute bioavailability of the sublingual fentanyl wafer was 78.9% (90% confidence interval [CI] 51.1% to 121.7%). The first detectable plasma fentanyl concentration time ranged from 2 to 10 minutes in all volunteers, and the mean (+/- SD) time to peak plasma concentration at 0.91 (+/- 0.73) hours after administration. CONCLUSION: Sublingual administration of fentanyl as a wafer product resulted in rapidly detectable plasma fentanyl concentrations. The absolute bioavailability of 78.9% indicated a high systemic availability of fentanyl and suggests that further development of this wafer is justified. (Anesth Analg 2012;115:554-9)