PHARMACOKINETICS OF INTRANASAL ALFENTANIL

Study Objective: To determine the pharmacokinetics of intranasal and intravenous (IV) administrations of alfentanil in 10 healthy volunteers. Design: Randomized, prospective, double-blind, placebo-controlled, cross-over trial with at least one week between the two modes of administration. Setting: Healthy volunteers at a university medical center. Subjects: 10 healthy, nondrug-dependent volunteers. Interventions: Alfentanil 0.54 mg was administered either intranasally [with 12 ml of sodium chloride (NaCl) 0.9% IV] or IV (with 12 sprays of NaCl 0.9% intranasally). Each subject was assigned once to the intranasal and once to the IV group. To guar antee a complete elimination of alfentanil, there was a time period of at least one week between the different modes of administration. Measurements and Main Results: Venous blood was sampled from a cubital vein at 3, 6, 9, 12, 15, 20, 30, 60, and 120 minutes after administration. Alfentanil plasma concentrations were determined by radioimmunoassay. Maximal plasma concentrations were 20.1 ng/ml +/- 7.3 ng/ml after 9 minutes in the intranasal group. At this measurement 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 was 64.96% +/- 26.3%. Conclusions: This pharmacokinetic study demonstrates a rapid rise in plasma concentrations, as well as a high bioavailability, following the intranasal administration of alfentanil.