マキハラ　ヒロコ   MAKIHARA Hiroko   槇原　弘子    所属   医学部 医学科    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Effect of changes in skin properties due to diabetes mellitus on the titration period of transdermal fentanyl: single-center retrospective study and diabetic animal model study.
掲載誌名	正式名：Journal of pharmaceutical health care and sciences 略　 称：J Pharm Health Care Sci ISSNコード：20550294/20550294
掲載区分	国外
巻・号・頁	10(1),pp.80
著者・共著者	Mizuno Satoshi†, Takabayashi Makiko, Makihara Hiroko, Ogai Kazuhiro, Tsukui Kei, Ito Yuriko, Kawakami Takahiro, Hara Yusuke, Fujita Arimi, Tokudome Yoshihiro, Akase Tomoko, Kato Yukio, Shimada Tsutomu, Sai Yoshimichi*
発行年月	2024/12
概要	BACKGROUND:In the dose titration of transdermal fentanyl to prevent unrelieved pain, it is important to consider not only dose adjustment, but also the titration period, which is influenced by the time required to reach the steady state. Many patients with cancer pain experience comorbidities that might affect the skin properties and influence transdermal absorption. We hypothesized that skin changes due to diabetes mellitus (DM) would affect the titration period of transdermal fentanyl. We conducted a retrospective study and diabetic animal model study to test this hypothesis.METHODS:In the retrospective study, the titration period was defined in terms of "dose change" and "number of rescue opioids" in patients initiated on transdermal fentanyl. Multiple logistic regression analysis was performed to analyze the relation between the titration period and comorbidities, including DM. In the diabetic animal model study, intercellular lipids of stratum corneum (SC) were analyzed in Goto-Kakizaki (GK) rats, a model of DM, and the pharmacokinetics of intravenously or transdermally administered fentanyl was examined.RESULTS:In the retrospective study, the titration period ranged from 5 to 39 days (n = 387), and the patients taking a longer period (6 days or more) was significantly related to in patients with unspecified DM: AOR (95% confidence interval), 0.438 (0.217-0.884). In the diabetic animal model study, the ceramides (CERs) content in the SC was decreased by approximately 30% in GK rats compared to Wistar rats. The absorption rate constant (ka) of fentanyl administered transdermally was increased approximately 1.4-fold in GK rats, though there was no difference in transdermal bioavailability (F) or systemic clearance (CLtot).CONCLUSION:Our results suggest that the steady state of transdermally administered fentanyl is reached sooner in cancer patients with DM as a comorbidity. Earlier pain assessment and dose adjustment may be possible in these patients.
DOI	10.1186/s40780-024-00402-5
PMID	39696707