Effect of obesity on pharmacokinetics of transdermal fentanyl: Single-center retrospective study and animal study

A retrospective study and an animal study were conducted to investigate factors affecting the transdermal fentanyl dose to achieve adequate pain relief in patients switched from other opioids. In the retrospective study, patient factors were included as gender, age, body mass index (BMI), and serum albumin concentration. In obese (BMI ≥25) patients, the post-titration dose of transdermal fentanyl was significantly lower than in normal (BMI 18.5-25) patients despite the initial dose was the same. To support this unexpected finding, fentanyl was administered intravenously and transdermally to Zucker (fa/fa) rats as an obese model and Zucker (+/+) rats as a control. No difference in systemic clearance (CL_tot) after intravenous administration was observed between the two groups. However, transdermal bioavailability (F) and fentanyl release ratio from the formulation (F_a) were significantly increased in Zucker (fa/fa) rats compared to Zucker (+/+) rats. Skin availability (F_skin), calculated as F divided by F_a, was also significantly increased. These results indicated that obesity should be considered as a factor in the titration of transdermal fentanyl dose.