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

IF 2.7 4区医学 Q2 PHARMACOLOGY & PHARMACY Drug Metabolism and Pharmacokinetics Pub Date : 2025-02-01 DOI:10.1016/j.dmpk.2024.101035

Satoshi Mizuno , Shintaro Gake , Makiko Takabayashi , Yuriko Ito , Hiroko Sanada , Natsumi Sugimoto , Akari Maeda , Takuto Tamamura , Kazuki Sawamoto , Yusuke Hara , Yoshiko Ohi , Chiaki Tsuji , Yukiko Shiomoto , Yukio Kato , Arimi Fujita , Tsutomu Shimada , Ken-ichi Miyamoto , Yoshimichi Sai

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Abstract

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.

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肥胖对芬太尼透皮药代动力学的影响：单中心回顾性研究和动物研究。

我们进行了一项回顾性研究和一项动物研究，以调查影响经皮芬太尼剂量的因素，以实现从其他阿片类药物切换的患者充分缓解疼痛。在回顾性研究中，患者因素包括性别、年龄、体重指数（BMI）和血清白蛋白浓度。在肥胖（BMI≥25）患者中，尽管初始剂量相同，经皮芬太尼滴药后剂量显著低于正常（BMI 18.5-25）患者。为了支持这一意想不到的发现，芬太尼被静脉注射和经皮给药给Zucker （fa/fa）大鼠作为肥胖模型，Zucker（+/+）大鼠作为对照。两组静脉给药后的全身清除率（CLtot）无差异。然而，与Zucker（+/+）大鼠相比，Zucker （Fa / Fa）大鼠的透皮生物利用度(F)和芬太尼释放比（Fa）显著增加。皮肤有效度（Fskin）（以F / Fa计算）也显著增加。这些结果表明，在芬太尼透皮剂量的滴定中应考虑肥胖因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Metabolism and Pharmacokinetics 医学-药学

CiteScore

4.80

自引率

9.50%

发文量

审稿时长

69 days

期刊介绍： DMPK publishes original and innovative scientific papers that address topics broadly related to xenobiotics. The term xenobiotic includes medicinal as well as environmental and agricultural chemicals and macromolecules. The journal is organized into sections as follows: - Drug metabolism / Biotransformation - Pharmacokinetics and pharmacodynamics - Toxicokinetics and toxicodynamics - Drug-drug interaction / Drug-food interaction - Mechanism of drug absorption and disposition (including transporter) - Drug delivery system - Clinical pharmacy and pharmacology - Analytical method - Factors affecting drug metabolism and transport - Expression of genes for drug-metabolizing enzymes and transporters - Pharmacogenetics and pharmacogenomics - Pharmacoepidemiology.