title: Single-dose and steady-state pharmacokinetics of fentanyl buccal tablet in healthy volunteers.
abstract: This study evaluated the single-dose and steady-state pharmacokinetics of fentanyl buccal tablet 400 microg in healthy adult volunteers. After receiving naltrexone 50 mg to block opioid receptor-mediated effects of fentanyl, subjects received fentanyl buccal tablet 400 microg on day 1, then every 6 hours from day 4 to day 9 (21 doses). Naltrexone 50 mg was administered every 12 hours throughout the study. Plasma fentanyl concentrations were determined for 72 hours after administration of fentanyl buccal tablet 400 microg on day 1 and the last dose of fentanyl buccal tablet 400 microg on day 9. Following single- and multiple-dose administration of fentanyl buccal tablet, the median time to maximum concentration (tmax) was 52.2 and 49.8 minutes, respectively. Peak plasma concentration of fentanyl (Cmax) was 0.88 ng/mL for the single-dose regimen and 1.77 ng/mL for the multiple-dose regimen. Steady state was reached within 5 days, consistent with the observed median half-life of approximately 22 hours following multiple doses. Observed accumulation of fentanyl after multiple doses of fentanyl buccal tablet was slightly greater than would be expected based on the single-dose data. This was attributed to the redistribution of fentanyl from a deep tissue compartment into the plasma. This study indicates that fentanyl buccal tablet has predictable pharmacokinetics following multiple-dose administration.
authors.affiliation: Clinical Pharmacology, Cephalon, Inc., Frazer, Pennsylvania, USA. mdarwish@cephalon.com
authors.forename: Mona
authors.initials: M
authors.lastname: Darwish
authors.forename: Mary
authors.initials: M
authors.lastname: Kirby
authors.forename: Philmore
authors.initials: P
authors.lastname: Robertson
authors.forename: Edward
authors.initials: E
authors.lastname: Hellriegel
authors.forename: John G
authors.initials: JG
authors.lastname: Jiang
mesh_terms: D000278:Administration, Buccal; D000293:Adolescent; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D004361:Drug Tolerance; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D013607:Tablets; D009271:Naltrexone; D005283:Fentanyl