Pharmacokinetics of fentanyl in male and female rats after intravenous administration

The sex difference of fentanyl (CAS 99073-8) pharmacokinetics was investigated after intravenous administration to male and female rats at a dose of 0.03 mg/kg. The plasma concentrations of fentanyl disappeared mono-phasically in both male and female rats. Plasma concentrations and pharmacokinetic parameters were not significantly different in male and female rats, but plasma concentrations of fentanyl in female rats were lower than those in male rats until 1 h after administration. The distribution volume in female rats was 1.34 times larger than that in male rats. In a previous study, the C-max and AUC(0-infinity) values in female rats were significantly lower than those in male rats after subcutaneous administration of fentanyl. Since no sex difference in the pharmacokinetic parameters of fentanyl were observed after intravenous administration in the present study, the sex difference of the pharmacokinetics of fentanyl after subcutaneous administration may be explained by delayed distribution from the dosing site to the systemic circulation in female rats relative to male rats, which may be attributable to a higher content of subcutaneous fat in female rats.