PHARMACOKINETICS OF INTRANASAL ALFENTANIL

Study Objective: To determine the pharmacokinetics of intranasal and i ntravenous (IV) administrations of alfentanil in 10 healthy volunteers . Design: Randomized, prospective, double-blind, placebo-controlled, c ross-over trial with at least one week between the two modes of admini stration. Setting: Healthy volunteers at a university medical center. Subjects: 10 healthy, nondrug-dependent volunteers. Interventions: Alf entanil 0.54 mg was administered either intranasally [with 12 ml of so dium chloride (NaCl) 0.9% IV] or IV (with 12 sprays of NaCl 0.9% intra nasally). Each subject was assigned once to the intranasal and once to the IV group. To guar antee a complete elimination of alfentanil, the re was a time period of at least one week between the different modes of administration. Measurements and Main Results: Venous blood was sam pled from a cubital vein at 3, 6, 9, 12, 15, 20, 30, 60, and 120 minut es after administration. Alfentanil plasma concentrations were determi ned by radioimmunoassay. Maximal plasma concentrations were 20.1 ng/ml +/- 7.3 ng/ml after 9 minutes in the intranasal group. At this measur ement point, the intranasal alfentanil concentrations were 64.7% (18.7 ng/ml +/- 6.8 ng/ml) of the IV concentrations (28.9 ng/ml +/- 7.9 ng/ ml). The calculated bioavailability after intranasal administration wa s 64.96% +/- 26.3%. Conclusions: This pharmacokinetic study demonstrat es a rapid rise in plasma concentrations, as well as a high bioavailab ility, following the intranasal administration of alfentanil.