True nasopharyngeal absorption of zolmitriptan after administration via nasal spray in healthy male volunteers

Objective

The aim of this study was to quantify the fraction of zolmitriptan that is absorbed directly through the nasal mucosa after administration of zolmitriptan nasal spray.

Methods

Following confirmation that activated charcoal blocks gastrointestinal absorption of zolmitriptan, healthy male volunteers were given zolmitriptan nasal spray 5mg (with and without charcoal) and zolmitriptan 5mg oral tablets (with and without charcoal) in a randomized, crossover design. Blood samples for pharmacokinetic analysis were collected up to 9 hours post-dose. Twelve subjects completed all treatments.

Results

The fraction of bioavailable dose absorbed through the nasal mucosa was calculated to be 29% (95% CI 19, 43). Intranasal absorption contributed 71% of zolmitriptan exposure during the first hour post-dose and 49% during the first 2 hours.

Conclusions

This study confirms true nasopharyngeal absorption of zolmitriptan after nasal spray administration. This route of absorption contributed approximately 30% of total zolmitriptan exposure, with much higher proportions of exposure seen during the first 2 hours post-dose when patients would expect to benefit from treatment. These results suggest that intranasal absorption plays an important role in the early onset of efficacy of zolmitriptan nasal spray seen in clinical trials.