ArticleDrug metabolism and disposition: the biological fate of chemicals2026
Pharmacokinetics of repeated, high-dose fentanyl administration in rats.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Fentanyl is a potent synthetic opioid widely used as a recreational drug. It is primarily metabolized in the liver to the inactive compound norfentanyl, with only a small fraction excreted unchanged via the kidneys. However, it remains unclear whether repeated high-dose exposure alters its pharmacokinetics (PK) over time. This study evaluated the effects of repeated high-dose fentanyl administration on PK and assessed sex-related differences in metabolism. Male and female Sprague-Dawley rats (n = 19) received intravenous boluses of 100 μg/kg fentanyl twice weekly for 5 weeks. After the 1st, 5th, and 10th doses, plasma concentrations of fentanyl and norfentanyl were measured using ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. PK data were analyzed using noncompartmental methods, followed by covariate analysis within a population PK model and a physiologically based PK model to identify underlying physiological factors. Noncompartmental analysis showed significantly lower C
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