Pharmacokinetics of Fentanyl Following Intravenous and Oral Routes of Administration in Healthy Volunteers
Condition: Biological Availability
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study is to compare the pharmacokinetics of fentanyl following i.v. and
      oral administration in healthy volunteers, and to assess the bioavailability of fentanyl
      following oral administration. Moreover, safety is assessed.
    

Detailed description: 
      Fentanyl, is an opioid (morphine-like) drug, that has been demonstrated to be an effective
      pain-killer medication by the i.v. and transdermal (through skin) routes. Fentanyl is used
      just before, during, and after surgery for its sedative and pain-relieving actions. In
      addition, fentanyl is currently marketed for transdermal use (Duragesic fentanyl transdermal
      patch) for the management of chronic pain. The information on the bioavailability of fentanyl
      solution, following the oral route of administration, is sparse. This is a single-center,
      randomized (study drug assigned by chance), open-label, 2-treatment, 2-period, crossover
      study. Healthy volunteers were randomly assigned to 1 of the 2 treatment sequences (AB or BA)
      with a washout period of 6 to 14 days between treatments. The washout period commenced the
      day of dosing, after drug administration. Prior to the first treatment period, each healthy
      volunteer was challenged with naloxone to ensure that he/she was not dependent on
      morphine-like drugs. A negative naloxone challenge test was required for the healthy
      volunteer to be eligible for participation in the study. Each healthy volunteer received a 50
      mg naltrexone tablet starting 14 hours before dosing and then twice daily ending 24 hours
      after dosing to block the fentanyl effects. Blood samples were collected, from the arm
      opposite to the 1 selected for fentanyl i.v administration, for determination of blood
      fentanyl levels at the scheduled time points. Pulse, blood pressure, breathing rate, body
      temperature were recorded to monitor the safety. The healthy volunteers were monitored for
      respiratory depression every 30 minutes during sleep periods. The healthy volunteers remained
      in the clinic throughout the blood sample collection periods, and were monitored for adverse
      events throughout the study.

      Treatment A: 300 mcg fentanyl citrate administered i.v. over 15 minutes. The 300 mcg (6 mL)
      i.v. solution was diluted and infused at a rate of 1 mL/minute. Treatment B: 1 mg fentanyl
      citrate solution administered orally. One mg fentanyl citrate was ingested in 20 mL solution;
      Naltrexone (50 mg) was administered orally to each healthy volunteer in both periods starting
      14 hours before dosing, and twice daily through 24 hours post-dose.
    

Intervention name(s): Fentanyl citrate; Naltrexone; Naloxone
Intervention type(s): Drug
Intervention MeSH terms: Fentanyl; Naltrexone; Naloxone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Pharmacokinetics; Administration, Oral; Naltrexone; Biological Availability; Infusions, Intravenous; Fentanyl; Safety; Naloxone