The pharmacokinetics and tolerability of the oral neuraminidase inhibitor oseltamivir (Ro 64-0796/GS4104) in healthy adult and elderly volunteers

The tolerability and pharmacokinetics of Ro 64-0802, a potent, selective in hibitor of influenza neuraminidase, and ifs oral prodrug oseltamivir were i nvestigated in three double-blind, placebo-controlled studies. Two studies involved healthy adult volunteers (18-55 years) (n = 48) who received singl e (20-1000 mg) or bid doses (50-500 mg) (n = 32) of oseltamivir or placebo for 7 days. Healthy elderly volunteers (greater than or equal to 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 appea red rapidly in plasma and were significantly higher and longer lasting than those of oseltamivir. Pharmacokinetics of both compounds lwere linear. Mul tiple-dose exposure was predictable from single-dose data, and steady-state plasma concentrations were achieved within 3 days of bid drug administrati on. Oseltamivir was well tolerated at single doses of up to 1000 mg and twi ce-daily doses of up to 500 mg. Adverse events were mild in intensity. Expo sure to both prodrug and active metabolite was increased in elderly patient s by approximately 25%. However, due to the wide safety margin of both comp ounds, no dose adjustment is necessary for elderly patients. (C) 2000 the A merican College of Clinical Pharmacology.