Pharmacokinetics of Fentanyl Buccal Tablet: A Pooled Analysis and Review

Fentanyl buccal tablet (FBT) is indicated for the treatment of breakthrough pain in patients who are already receiving and are tolerant to opioid therapy for underlying, persistent cancer pain. FBT is designed to enhance the rate and efficiency of absorption of fentanyl through the buccal mucosa. FBT was shown to be dose proportional from 100 to 1,300 mu g. This analysis provides an overview of the pharmacokinetic profile of FBT based on pooled data from nine pharmacokinetic studies. In all, 365 healthy non-opioid-tolerant adults receiving naltrexone were included in the analysis. Single-dose (100 to 1,300 mu g) pharmacokinetic parameters were dose normalized to 100 mu g. Pharmacokinetic measures included maximum observed plasma drug concentration (Cmax), plasma drug concentration versus time curve from time zero to infinity (AUC08), time to reach Cmax (Tmax), apparent plasma terminal elimination rate constant, and elimination half-life. After FBT administration, fentanyl was rapidly absorbed, with Tmax ranging from 20 minutes to 4 hours postdose. Mean AUC08 was 1.49 nghour/mL, and mean Cmax was 0.237 ng/mL. However, plasma fentanyl concentration reached 80% of Cmax within 25 minutes and was maintained through 2 hours after administration. Based on the individual studies, bioequivalence was shown for sublingual and buccal tablet placement, and no significant effect of dwell time (duration of FBT presence in the oral cavity) was observed. The pharmacokinetic profile of FBT was characterized by rapid absorption, which is consistent with the rapid-onset efficacy profile of FBT observed in clinical studies.