Publication: Pharmacological Reports
Abstract
Critically ill patients frequently develop hypothermia from sepsis, trauma, or environmental exposure, which can alter drug disposition, yet the effect on fentanyl pharmacokinetics has not been well defined. This study compared fentanyl and norfentanyl pharmacokinetics in Wistar rats exposed to moderate (30°C) or severe (27°C) environmentally induced hypothermia versus normothermic controls following intravenous fentanyl administration, with concentrations measured by LC-ESI-MS/MS and parameters calculated using Phoenix WinNonlin. Severe hypothermia significantly increased fentanyl Cmax and AUC while reducing clearance by 44% and decreasing volume of distribution, with norfentanyl exposure also increased across all measured parameters; moderate hypothermia produced smaller, more limited changes. The results demonstrate that hypothermia alters fentanyl and norfentanyl pharmacokinetics in a temperature-dependent manner, which may have implications for opioid dosing in hypothermic critically ill patients.
Author(s): Stach P, Skowron K, Rojek S, Cios A, Wesołowska A, Huestis MA, Gil K
Published: 2026 年 1 月 23 日
Phoenix WinNonlin: Temperature-Dependent PK
Phoenix WinNonlin quantified how hypothermia altered fentanyl and norfentanyl exposure in this preclinical study, the kind of temperature-dependent shift that matters for critically ill patients. Phoenix WinNonlin is the gold standard engine for noncompartmental analysis, PK/PD, and toxicokinetic modeling, part of a Phoenix platform that centralizes data, analyses, and templates with built-in collaboration.
