A review of the pharmacokinetic profile of transmucosal fentanyl formulations

Curr Med Res Opin. 2012 Nov;28(11):1781-90. doi: 10.1185/03007995.2012.735227. Epub 2012 Oct 18.


Background and objectives: Breakthrough pain (BTP) is a transitory flare of moderate-to-severe pain that occurs in patients with stable, controlled persistent pain. Management of BTP episodes is difficult because frequency, time-to-peak intensity, and duration of episodes vary both within and between individuals. Formulations of fentanyl that use a buccal, sublingual, or nasal transmucosal route of administration have been developed for the treatment of BTP in opioid-tolerant patients with cancer. These formulations allow rapid passage into the bloodstream and avoid first-pass metabolism and, therefore, are more likely to match the time-course of BTP episodes than are oral formulations. The purposes of this analysis were to identify and review published data describing the pharmacokinetic properties of rapid-onset fentanyl formulations and to evaluate these properties in view of the temporal dynamic characteristics of BTP in order to help guide medical practice.

Methods: Relevant publications were searched in the PubMed database from 1998. The plasma drug concentration-time profile of each formulation obtained from the identified studies was adjusted to a consistent scale for comparison.

Results: The data revealed that the various transmucosal formulations resulted in three typical plasma fentanyl concentration profiles: (1) type 1: a very rapid rise and short duration; (2) type 2: a rapid increase and sustained intensity; and (3) type 3: a slower onset and longer duration.

Conclusions: Given the substantial variability of BTP episodes experienced by patients, these pharmacokinetic differences may provide useful information for a physician who is selecting a rapid-onset opioid medication for a patient.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Oral
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacokinetics*
  • Analgesics, Opioid / therapeutic use
  • Fentanyl / administration & dosage
  • Fentanyl / pharmacokinetics*
  • Fentanyl / therapeutic use
  • Humans
  • Mouth Mucosa / metabolism*
  • Pain / drug therapy


  • Analgesics, Opioid
  • Fentanyl