Intra- and Interindividual Variabilities in the Pharmacokinetics of Fentanyl Buccal Soluble Film in Healthy Subjects

Background and Objective: Breakthrough pain describes transient exacerbations of pain that occur in cancer patients with adequately controlled background pain. Transmucosal fentanyl administration produces rapid-onset and short-duration analgesia that is effective for treating patients with breakthrough pain. Although a significant amount of research has been devoted to the study of speed of analgesia onset of transmucosal fentanyl products, few data exist on their variability in absorption, particularly within the same individual, despite the importance of this characteristic to the dose-to-dose reliability of their analgesic effect. This cross-study analysis aimed to evaluate the intra- and interindividual pharmacokinetic differences of fentanyl administered via fentanyl buccal soluble film in healthy subjects.

Methods: Data were evaluated from 24 subjects in two pharmacokinetic studies of fentanyl administered via fentanyl buccal soluble film (Breakyl®/Onsolis™; BEMA® [BioErodible MucoAdhesive] technology). In one study, 12 healthy subjects received 600 µg doses of fentanyl as single film on two separate occasions; in the second study, 12 different healthy subjects received 800 µg doses of fentanyl on two separate occasions, one as a single 800 µg film and the other as four 200 µg films.

Results: The analysis showed a minimal intraindividual variability and a relatively higher interindividual variability in pharmacokinetic parameters (i.e. maximum plasma concentration, area under the plasma concentration-time curve from time zero to infinity). The coefficient of variation for intraindividual exposure to fentanyl variability was 7–10%, and for interindividual variability was 23–39%.

Conclusion: The minimal intraindividual variability in fentanyl absorption from the buccal soluble film demonstrates a predictable dose-to-dose exposure, which is a very desirable attribute for a medicine that is intended to treat breakthrough cancer pain, suggesting that this product would be expected to produce consistent effects in clinical practice. The greater interindividual variability highlights the need for individual titration of this product (as occurs with similar transmucosal fentanyl products), and for the availability of an adequately wide dose range.