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Publications (1)4.57 Total impact

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    ABSTRACT: Zanamivir serum and pulmonary pharmacokinetics were characterized following intravenous (i.v.) or oral inhaled administration. I.v. zanamivir was given as intermittent doses of 100 mg, 200 mg, and 600 mg every 12 h (q12h) for two doses or as a continuous infusion (6-mg loading dose followed by 3 mg/h for 12 h). Oral inhaled zanamivir (two 5-mg inhalations q12h for two doses) was evaluated as well. Each zanamivir regimen was administered to six healthy subjects with serial pharmacokinetic sampling. In addition, a single bronchoalveolar lavage (BAL) fluid sample was collected at various time points and used to calculate epithelial lining fluid (ELF) drug concentrations for each subject. For intermittent i.v. administration of 100 mg, 200 mg, and 600 mg zanamivir, the median zanamivir concentrations in ELF collected 12 h after dosing were 74, 146, and 419 ng/ml, respectively, each higher than the historic mean 50% inhibitory concentrations for the neuraminidases of wild-type strains of influenza A and B viruses. Median ELF/serum zanamivir concentration ratios ranged from 55 to 79% for intermittent i.v. administration (when sampled 12 h after the last dose) and 43 to 45% for continuous infusion (when sampled 6 to 12 h after the start of the infusion). For oral inhaled zanamivir, the median zanamivir concentrations in ELF were 891 ng/ml for the first BAL fluid collection and 326 ng/ml for subsequent BAL fluid collections (when sampled 12 h after the last dose); corresponding serum drug concentrations were undetectable. This study demonstrates zanamivir's penetration into the human pulmonary compartment and supports the doses selected for the continuing development of i.v. zanamivir in clinical studies of influenza.
    Antimicrobial Agents and Chemotherapy 09/2011; 55(11):5178-84. · 4.57 Impact Factor