Pharmacological and pharmacokinetic study of Isobutyryfentanyl in female and male CD1 Mice

Despite the decline of fentanyl and its analogs seizure in Europe, these synthetic opioids continue to be detected in many cases of death. Moreover, there is a scarce literature regarding the pharmacology and the pharmacokinetic of these drugs. This study is aimed to i) assess the in vivo pharmacological effects of the fentanyl analog Isobutyrylfentanyl (IBF) in male and female mice administered an intraperitoneal dose of 5 mg/kg, ii) determine the pharmacokinetic profiles in plasma, urine and tissues of both sexes, and iii) correlate the behavioral and physiological effects with IBF plasma levels in males and females. Sex differences were observed in the behavioral and pharmacokinetic effects of IBF. IBF showed a persistent motor and analgesic effects after 24h of measurements. Females consistently exhibited more pronounced and longer-lasting responses, particularly in motor and sensorimotor tests, and showed slower drug elimination. In contrast, males demonstrated stronger responses in vibrissae reflex tests and had a faster clearance of IBF. These results underscore the importance of accounting for sex as a biological variable in pharmacological research, with potential implications for clinical and forensic applications.