Pharmacokinetics and tolerability of a single inhaled dose of zanamivir in children

Objective: The purpose of this study was to examine the pharmacokinetics, safety, and tolerability of zanamivir in children, Background: Zanamivir is a potent inhibitor of viral neuraminidase that is effective against both influenza A and B infections, Methods: A pediatric study was conducted to examine the pharmacokinetics, safety, and tolerability of zanamivir in children who had signs of respiratory illness. Twenty-four children aged 3 months to 12 years received zanamivir administered as a single, orally inhaled, 10-mg dose either by nebulizer (in patients <5 years of age) or by Diskhaler(R) (in patients greater than or equal to 5 years of age), Serum and urine zanamivir concentrations were analyzed both before dosing and from 0.5 to 8 hours after dosing, Results: The rate and extent of absorption of zanamivir were independent, of the inhalation formulation or of the patient's age, Median maximum serum concentrations were 47 ng/mL in younger patients (aged greater than or equal to 3 months to <5 years and greater than or equal to 5 to <9 years) and 40 ng/mL in older patients (aged greater than or equal to 9 to less than or equal to 12 years). These maximum concentrations were attained by 1.5 hours after dosing. Median values for area under the curve from 0 time after dosing to infinite time after dosing were 184 ng.h/mL in patients greater than or equal to 3 months to <5 years of age, 192 ng.h/mL in patients greater than or equal to 5 to <9 years of age, and 167 ng.h/mL in patients greater than or equal to 9 to less than or equal to 12 years of age. Less than 8% of the inhaled drug was excreted in urine as unchanged drug These results indicate a low bioavailability of zanamivir after pulmonary delivery and suggest that zanamivir is not metabolized in children before excretion, Adverse events observed in this: study were mild and resolved spontaneously, Conclusions: Results of the present study suggest that a 10-mg dose of zanamivir is safe and well tolerated when used in children who have signs and symptoms of respiratory illness.