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The Pharmacokinetics and Tolerability of the Oral Neuraminidase Inhibitor Oseltamivir (Ro 64–0796/GS4104) in Healthy Adult and Elderly Volunteers
Author(s) -
Massarella Joseph W.,
He George Z.,
Dorr Albert,
Nieforth Keith,
Ward Penelope,
Brown Andy
Publication year - 2000
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912700022009567
Subject(s) - pharmacokinetics , tolerability , oseltamivir , neuraminidase inhibitor , prodrug , placebo , pharmacology , active metabolite , medicine , adverse effect , metabolite , oral administration , pharmacodynamics , neuraminidase , immunology , virus , covid-19 , pathology , alternative medicine , disease , infectious disease (medical specialty)
The tolerability and pharmacokinetics of Ro 64–0802, a potent, selective inhibitor of influenza neuraminidase, and its oral prodrug oseltamivir were investigated in three double‐blind, placebo‐controlled studies. Two studies involved healthy adult volunteers (18–55 years) (n = 48) who received single (20–1000 mg) or bid doses (50–500 mg) (n = 32) of oseltamivir or placebo for 7 days. Healthy elderly volunteers (≥65 years) (n = 24) received oseltamivir 100 to 200 mg bid or placebo for 7 days in a third study. Measurable plasma concentrations of the active metabolite appeared rapidly in plasma and were significantly higher and longer lasting than those of oseltamivir. Pharmacokinetics of both compounds were linear. Multiple‐dose exposure was predictable from single‐dose data, and steady‐state plasma concentrations were achieved within 3 days of bid drug administration. Oseltamivir was well tolerated at single doses of up to 1000 mg and twice‐daily doses of up to 500 mg. Adverse events were mild in intensity. Exposure to both prodrug and active metabolite was increased in elderly patients by approximately 25%. However, due to the wide safety margin of both compounds, no dose adjustment is necessary for elderly patients.