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To date, pFF has not been extensively evaluated in vivo and is frequently seen in combination with fentanyl. In the present study, the pharmacodynamic (PD) and pharmacokinetic (PK) properties and brain region-specific concentrations of pFF were evaluated in male Sprague\u2013Dawley rats and compared to fentanyl. A 300\u00a0\u03bcg\/kg subcutaneous dose of fentanyl or pFF was administered to assess PD and PK parameters as well as brain region concentrations. PD parameters were evaluated via a tail flick test to evaluate analgesia and core body temperature to measure hypothermia, a surrogate marker of overall opioid toxicity. Fentanyl and pFF were found to be equally active at the tested dose in terms of tail flick response with both compounds producing an analgesic response that lasted up to 240\u00a0min post-drug treatment. pFF induced a significantly greater hypothermic effect compared to fentanyl with a maximum temperature decrease of \u22125.6 \u2103. Plasma PK parameters (T<jats:sub>1\/2<\/jats:sub>, AUC, etc.) did not differ between fentanyl and pFF. However, pFF concentrations in the medulla, hippocampus, frontal cortex and striatum were more than two times the fentanyl concentrations. The increase in brain concentrations and greater hypothermic effect suggests that pFF is potentially more dangerous than fentanyl.<\/jats:p>","DOI":"10.1007\/s00204-024-03887-z","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T16:03:34Z","timestamp":1729181014000},"page":"287-297","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["In vivo pharmacokinetic, pharmacodynamic and brain concentration comparison of fentanyl and para-fluorofentanyl in rats"],"prefix":"10.1007","volume":"99","author":[{"given":"Jeremy R.","family":"Canfield","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0349-5072","authenticated-orcid":false,"given":"Jon E.","family":"Sprague","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"3887_CR1","unstructured":"AAFS (American Academy of Forensic Sciences) Academy Standards Board, (2019) ANSI\/ASB Standard 036: Standard Practices for Method Validation in Forensic Toxicology, 1st Edition. 2019. 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