Early pharmacokinetics of nasal fentanyl: is there a significant arterio-venous difference?

Objective We have investigated the arterio-venous difference in the pharmacokinetics of 50 mu g fentanyl during the first hour following nasal administration and documented its tolerability in opioid-naive middle-aged to elderly patients. Methods Twelve male patients (range in age 47-84 years) scheduled for transurethral resection of the prostate gland received a 100-mu l dose of 50 mu g fentanyl base as a fentanyl citrate formulation in one nostril. Simultaneous arterial and venous blood samples for analyses of fentanyl were drawn at baseline and at 1, 3, 5, 7, 9, 13, 15, 20, 25, 35, 45 and 60 min after drug administration. Vital signs, sedation and symptoms of local irritation were recorded. Results The arterial C-max (maximum serum concentration) of 0.83 ng/ml was nearly twofold higher than the venous C-max of 0.47 ng/ml, and the arterial T-max (time to maximum serum concentration) of 7.0 min was about 5 min shorter than the venous T-max of 11.6 min. The arterial AUC(0-60) (area under the curve from 0 to 60 min after administration) of 21 min*ng/ml was approximately 30% larger than the venous AUC(0-60) of 15 min*ng/ml (all p values <= 0.005). Venous T-max and C-max did not predict the corresponding arterial values. No significant adverse events were observed. Conclusion A significant arterio-venous difference was present after intranasal administration of fentanyl. The short arterial T-max complies with its rapid onset of action. The use of venous concentrations for the prediction of onset time of analgesia should be discouraged. A 50-mu g dose of nasal fentanyl was well tolerated by opioid-naive middle-aged to elderly male patients.