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 microg fentanyl during the first hour following nasal administration and documented its tolerability in opioid-naïve 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-microl dose of 50 microg 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 < or = 0.005). Venous T(max) and C(max) did not predict the corresponding arterial values. No significant adverse events were observed.


CONCLUSIONS
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-microg dose of nasal fentanyl was well tolerated by opioid-naïve middle-aged to elderly male patients.
Moksnes
Kristin
K
Department of Circulation and Medical Imaging, Pain and Palliation Research Group, Norwegian University of Science and Technology, St. Olav University Hospital, Kreftbygget, 5th floor, Olav Kyrres gate 17, 7006, Trondheim, Norway. kristin.moksnes@ntnu.no
Fredheim
Olav M
OM
Klepstad
Pål
P
Kaasa
Stein
S
Angelsen
Anders
A
Nilsen
Turid
T
Dale
Ola
O
D000281:Administration, Intranasal; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001158:Arteries; D005283:Fentanyl / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D034941:Upper Extremity / Q000098:blood supply; D014680:Veins
D000701:Analgesics, Opioid; D005283:Fentanyl