Deposition and disposition of [11C]zanamivir following administration as an intranasal spray. Evaluation with positron emission tomography.
OBJECTIVE
This study used positron emission tomography (PET) to investigate the deposition and disposition of zanamivir administered as a nasal spray.


METHODS
This was an open-label single-dose study in healthy volunteers.


METHODS
Six healthy male volunteers, aged 19 to 33 years (mean age 25 years) with a bodyweight of 65 to 94 kg (mean bodyweight 76 kg), took part in the study.


METHODS
Each participant received by nasal spray zanamivir 6.4 mg mixed with, on average, 2.5 MBq of [11C]zanamivir. The amount of radioactivity was recorded sequentially in 5 different sectors of the body, starting with 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 were taken for analysis of radioactivity in whole blood. Serum samples for pharmacokinetic determinations were collected for 8 hours after administration.


RESULTS
Immediately after administration, about 90% of the drug was deposited in the nasal passage, decreasing to 48% at 90 minutes after administration. Less than 2% was detected in the lower respiratory tract. The major elimination route was via the oesophagus to the stomach. Approximately 2% of the dose was absorbed; the median maximum drug concentration in serum was 15 micrograms/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 least 1.5 hours after administration. PET seems to be an excellent tool for this type of kinetic study, allowing imaging and measurements of inhaled drugs with high quantitative accuracy and good spacial resolution.
Bergstrom
M
M
Uppsala University PET Centre, Sweden. Mats.Bergstrom@PET.UU.SE
Cass
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Valind
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Westerberg
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Lundberg
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Gray
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Bye
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A
Langstrom
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B
D000281:Administration, Intranasal; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D004341:Drug Evaluation; D004947:Esophagus / Q000000981:diagnostic imaging / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D006146:Guanidines; D006801:Humans; D008297:Male; D010614:Pharynx / Q000000981:diagnostic imaging / Q000378:metabolism*; D011714:Pyrans; D012016:Reference Values; D012794:Sialic Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013270:Stomach / Q000000981:diagnostic imaging; D014055:Tomography, Emission-Computed; D053243:Zanamivir
D000998:Antiviral Agents; D002250:Carbon Radioisotopes; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D053243:Zanamivir