Effect of Modulated Electrohyperthermia on the Pharmacokinetics of Oral Transmucosal Fentanyl Citrate in Healthy Volunteers

Purpose This study aimed to determine whether changes occur in fentanyl absorption and disposition when administered in conjunction with modulated electrohyperthermia (mEHT) treatment. Methods A randomized, single-dose, crossover, open-label study was used to investigate the effect of mEHT on the pharmacokinetic properties of fentanyl in 12 healthy volunteers. The 12 healthy volunteers were each administered a single dose of oral transmucosal fentanyl citrate (OTFC) or a single dose of OTFC with mEHT. mEHT was performed on the abdomen for 1 hour. Blood samples were collected for 24 hours after dosing. The temperature of the abdominal skin surface was assessed before dosing and at 10, 20, and 60 minutes after dosing. Findings Geometric mean ratios (ratio of fentanyl with mEHT to fentanyl alone) for the C_max and AUC_0–last were 1.20 (90% CI, 1.09–1.32) and 1.15 (90% CI, 0.99–1.33), respectively. The mean temperature of the abdominal skin surface increased by approximately 4°C. Implications There was an increase in the overall exposure to the drug without implications of any clinical significance. OTFC can be administered without limitations in combination with mEHT, and it is not necessary to modify the dosing regimen. cris.nih.go,kr Identifier: KCT0001286.