Deposition and disposition of [C-11]zanamivir following administration as an intranasal spray - Evaluation with positron emission tomography

Objective: This study used positron emission tomography (PET) to investigat e the deposition and disposition of zanamivir administered as a nasal spray . Design: This was an open-label single-dose study in healthy volunteers. Study participants: Six healthy male volunteers, aged 19 to 33 years (mean age 25 years) with a bodyweight of 65 to 94kg (mean bodyweight 76kg), took part in the study. Interventions: Each participant received by nasal spray zanamivir 6.4mg mix ed with, on average, 2.5 MBq of [C-11]zanamivir. The amount of radioactivit y was recorded sequentially in 5 different sectors of the body, starting wi th a short dynamic sequence over the nasal passage. Each of the regions was examined 1 to 4 times at different times after inhalation. The duration of the examination was 90 minutes. During this time, multiple blood samples w ere taken for analysis of radioactivity in whole blood. Serum samples for p harmacokinetic determinations were collected for 8 hours after administrati on. Results: Immediately after administration, about 90% of the drug was deposi ted in the nasal passage, decreasing to 48% at 90 minutes after administrat ion. Less than 2% was detected in the lower respiratory tract. The major el imination route was via the oesophagus to the stomach. Approximately 2% of the dose was absorbed; the median maximum drug concentration in serum was 1 5 mu g/L, and occurred around 1.75 hours after inhalation. Conclusions: The major deposition site for zanamivir administered by nasal inhalation is the nasal passage; half of the drug remains there for at leas t 1.5 hours after administration. PET seems to be an excellent tool for thi s type of kinetic study, allowing imaging and measurements of inhaled drugs with high quantitative accuracy and good spacial resolution.