Uptake pharmacokinetics of the Fentanyl Oralet® in children scheduled for central venous access removal: Implications for the timing of initiating painful procedures

Background: The Fentanyl Oralet® (Abbott Laboratories, Abbott Park, IL, USA) is an oral transmucosal drug delivery system. We previously examined pharmacokinetic parameters of children who had completed consumption of the Fentanyl Oralet®. The present study was designed to clarify pharmacokinetic parameters during the consumption phase to determine if there is an optimal administration time before painful procedures. Methods: Patients, aged 3-10 years, who were scheduled for elective removal of central venous access devices under general anaesthesia, received a Fentanyl Oralet® (fentanyl 10-15 μg·kg^-1). Plasma fentanyl concentrations were measured by radioimmunoassay. Data from blood samples obtained during and after consumption of the Fentanyl Oralet® from 17 patients in the present study were combined with data from our previous study to better characterize both the consumption and postconsumption concentration versus time profiles. Results: Estimated fentanyl bioavailability (mean ± SD) was low (36.1 ± 0.4%), as were peak plasma concentrations (1.03 ± 0.31 ng·ml^-1), suggesting that many children swallowed a large fraction of the dose. This led to a relatively late and variable peak concentration time of 53 ± 40 min. In addition, because of the apparently large degree of gastrointestinal absorption, concentration versus time curves were wide and flat. Conclusions: The wide and flat concentration versus time profile may allow flexibility in the timing of a painful procedure following Fentanyl Oralet® administration. However, the variability of the time to peak concentration makes it difficult to suggest a minimum interval between Fentanyl Oralet® consumption and the start of a painful procedure.