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Background and Objective <p>Epidural sufentanil is widely used for intraoperative analgesia and is recognized as a safe and effective route of administration when carefully monitored and administered at the lowest effective doses. Optimizing drug dosing requires a precise understanding of its pharmacokinetics. While it is known that sufentanil concentrations in the blood decline more slowly after epidural administration compared with intravenous administration, and the flip-flop phenomenon has been observed in this context, a pharmacokinetic model accounting for this phenomenon has not yet been described.</p> Methods <p>This study aimed to develop a pharmacokinetic model of sufentanil following epidural administration, with a focus on its absorption from the epidural space. The study was performed in 23 patients, aged 30–83&#xa0;years with an American Society of Anesthesiologists (ASA) classification of 2–3, undergoing major abdominal (oncologic and non-oncologic) surgery under general anesthesia and epidural analgesia. Blood samples were collected, and sufentanil concentrations were measured at time points ensuring coverage of the absorption phase. Population analysis was performed using a full Bayesian approach implemented in Stan/Torsten programs with the “cmdstanr” and “bbr.bayes” packages in RStudio.</p> Results <p>The Bayesian approach helped incorporate prior information about sufentanil disposition. A two-compartment disposition model with two-compartmental absorption best described the data, featuring a fast absorption rate constant into plasma and the peripheral compartment, and a slow redistribution process from the epidural fat compartment.</p> Conclusions <p>This study mechanistically describes the flip-flop pharmacokinetics of sufentanil and allows for more precise dosing of epidural sufentanil (NCT06069219).</p>

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Pharmacokinetics of Sufentanil After Epidural Administration During the Course of Extensive Abdominal Surgery

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月29日

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  • Agnieszka Bienert,
  • Agnieszka Borsuk-De Moor,
  • Paulina Okuńska,
  • Justyna Ber,
  • Danuta Siluk,
  • Małgorzata Waszczuk,
  • Krzysztof Kusza,
  • Tomasz Bartkowiak,
  • Jakub Szrama,
  • Anna Kluzik,
  • Tomasz Koszel,
  • Paweł Wiczling

摘要

Background and Objective

Epidural sufentanil is widely used for intraoperative analgesia and is recognized as a safe and effective route of administration when carefully monitored and administered at the lowest effective doses. Optimizing drug dosing requires a precise understanding of its pharmacokinetics. While it is known that sufentanil concentrations in the blood decline more slowly after epidural administration compared with intravenous administration, and the flip-flop phenomenon has been observed in this context, a pharmacokinetic model accounting for this phenomenon has not yet been described.

Methods

This study aimed to develop a pharmacokinetic model of sufentanil following epidural administration, with a focus on its absorption from the epidural space. The study was performed in 23 patients, aged 30–83 years with an American Society of Anesthesiologists (ASA) classification of 2–3, undergoing major abdominal (oncologic and non-oncologic) surgery under general anesthesia and epidural analgesia. Blood samples were collected, and sufentanil concentrations were measured at time points ensuring coverage of the absorption phase. Population analysis was performed using a full Bayesian approach implemented in Stan/Torsten programs with the “cmdstanr” and “bbr.bayes” packages in RStudio.

Results

The Bayesian approach helped incorporate prior information about sufentanil disposition. A two-compartment disposition model with two-compartmental absorption best described the data, featuring a fast absorption rate constant into plasma and the peripheral compartment, and a slow redistribution process from the epidural fat compartment.

Conclusions

This study mechanistically describes the flip-flop pharmacokinetics of sufentanil and allows for more precise dosing of epidural sufentanil (NCT06069219).