Influence of carbon side chain length on the in vivo pharmacokinetic and pharmacodynamic characteristics of illicitly manufactured fentanyls

Five non-pharmaceutical fentanyls (NPF) were tested in a rat model to determine pharmacokinetic and pharmacodynamic profile differences. Fentanyl displayed the greatest analgesic and hypothermic effect of all compounds. Acetylfentanyl was the only compound that displayed pharmacokinetic differences from the other NPF, with a shorter half-life, area under the curve and maximum concentration. AbstractSince 2016, illicitly manufactured fentanyls and fentanyl analogs (referred to as IMFs) have contributed to an increase in drug overdoses. Although fentanyl has been characterized and evaluated extensively in animals and humans, many of the clandestinely synthesized analogs of fentanyl have not and users may unknowingly ingest these IMFs leading to overdose and potentially death. The pharmacodynamic (PD) and pharmacokinetic (PK) properties of four IMFs and fentanyl were evaluated in Sprague –Dawley rats. A 300-μg/kg subcutaneous dose of each compound (fentanyl, acetylfentanyl, cyclopropylfentanyl, butyrylfentanyl, and valerylfentanyl) was given. PD parameters were measured using a tail flick meter and core body temperature. Blood was drawn to evaluate PK parameters utilizing liquid chromatography tandem mass spectrometry (LC–MS/MS). Fentanyl displayed the greatest and longest lasting analgesia with a tail flick response of 10 s (the maximum cutoff). Additionally, fentanyl produced an average −4.9°C in core body temperature resulting in the greatest decrease in core body te...
Source: Drug Testing and Analysis - Category: Drugs & Pharmacology Authors: Tags: RESEARCH ARTICLE Source Type: research