Early pharmacokinetics of nasal fentanyl: is there a significant arterio-venous difference?
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We have investigated the arterio–venous difference in the pharmacokinetics of 50 μg fentanyl during the first hour following nasal administration and documented its tolerability in opioid-naïve middle-aged to elderly patients.
Twelve male patients (range in age 47–84 years) scheduled for transurethral resection of the prostate gland received a 100-μl dose of 50 μg 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.
The arterial Cmax (maximum serum concentration) of 0.83 ng/ml was nearly twofold higher than the venous Cmax of 0.47 ng/ml, and the arterial Tmax (time to maximum serum concentration) of 7.0 min was about 5 min shorter than the venous Tmax of 11.6 min. The arterial AUC0-60 (area under the curve from 0 to 60 min after administration) of 21 min*ng/ml was approximately 30% larger than the venous AUC0-60 of 15 min*ng/ml (all p values ≤ 0.005). Venous Tmax and Cmax did not predict the corresponding arterial values. No significant adverse events were observed.
A significant arterio–venous difference was present after intranasal administration of fentanyl. The short arterial Tmax 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-μg dose of nasal fentanyl was well tolerated by opioid-naïve middle-aged to elderly male patients.
KeywordsFentanyl Nasal Opioids Pain Pharmacokinetics Safety
The authors wish to thank Anette Arnberg, Pharm D, for the supply of nasal fentanyl from Nycomed Pharma. We are also grateful to Gunnhild Jakobsen R.N, and Anne Marie Lund M.Sc., for help with the data collection, Mari Sandrød Owesen R.N., for the recruitment of patients, Trine N. Andreassen M.Sc., for the opioid analyses, Johan Arnt Hegvik M.D., for cannulation and the staff at Recovery Unit and the Department of Urology for various assistance. We want to thank The Research Council of Norway and The Norwegian Cancer Society (E06096/002) for financial support. The study complies with the current Norwegian legislation.
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