Effect of viscosity on the pharmacokinetics and biological response to intranasal desmopressin

The effect of viscosity on the nasal absorption and biological response to desmopressin was studied in humans. Nasal solutions of desmopressin with and without the addition of 0.25% (w/v) methylcellulose were administered by a precompression nasal spray pump to 10 volunteers. Plasma levels of desmopressin were assayed by radioimmunoassay and the biological response was measured by determination of the antihemophilia factors (Factor VIII and von Willebrand factor). The results showed that the addition of methylcellulose produced a more sustained and slower absorption, with a longer time to maximum plasma concentration (tmax). However, the areas under the plasma concentration-time curve were not different, indicating a similar total bioavailability. The biological response showed a similar effect. Peak Factor VIII activity was not different, but the presence of methylcellulose produced a slower onset of activity. These findings indicate that although the addition of a viscous agent to nasal formulations may produce a more sustained effect, it delays the onset of activity and no enhancement is achieved in the total bioavailability.