2019 年 45 巻 7 号 p. 416-422
The bioavailability (BA) of commercially available fentanyl transdermal tape (CA-fentanyl tape) is enhanced under pyrexia. However, the contribution of drug release from the formulation and drug skin penetration in the enhanced BA has not yet been reported. In this study, we investigated the mechanism of drug penetration in CA-fentanyl tape by using a Franz diffusion cell set 0.45-μm membrane filter (drug release test) or rat abdominal skin (skin permeation test) at temperatures of 37℃ (normal) and 42℃ (hyperthermia). No difference in the drug release was observed between the 37℃ and 42℃ conditions, and the fentanyl in the formulation was completely released into the reservoir chamber at 9 h under both temperatures. Moreover, the amounts of fentanyl in the skin were also similar at 37℃ and 42℃. In contrast to the results in drug release and retention, the skin penetration at 42℃ was significantly higher than that at 37℃, and the area under the drug concentration-time curve (AUC0-30) at 37℃ and 42℃ were 3.13 ± 0.03 µmol∙h/cm2, 3.73 ± 0.14 µmol∙h/cm2, respectively. In conclusion, we found that the drug release from CA-fentanyl tape was not changed, although skin permeation was enhanced under mild hyperthermia (42℃) resulting in the enhancement of BA. These results provide useful information for the application of CA-fentanyl tape in the clinical setting.