Pharmacokinetics and safety of coadministered oseltamivir and rimantadine in
healthy volunteers: an open-label, multiple-dose, randomized, crossover study.
Author(s): Cirrincione-Dall G, Brennan BJ, Ballester-Sanchis RM, Navarro MT, Davies BE.
Affiliation(s): Hoffmann-La Roche, Inc, Nutley, NJ, USA.
Publication date & source: 2012, J Clin Pharmacol. , 52(8):1255-64
Preclinical data suggest increased antiviral activity and less viral resistance
when neuraminidase inhibitors and adamantanes are used in combination to harness
the complementary effects of their different mechanisms of action. Healthy
volunteers were randomized to 5-day oral treatment with oseltamivir 75 mg or
rimantadine 100 mg twice daily as monotherapy or to combination treatment. Each
participant received all 3 regimens in 1 of 6 treatment sequences, with a minimum
of 7 days' washout between periods. Final follow-up was 10 to 14 days after the
final dose. Drug exposure, elimination, safety, and tolerability were assessed.
There were no clinically relevant differences in 12-hour areas under the
concentration-time curves of drug in plasma or peak plasma drug concentrations
with combination versus monotherapy. Elimination half-life was unaffected by
coadministration. There were no safety/tolerability concerns. One case of
vomiting and 1 of paresthesia were considered remotely related to combination
treatment, and 1 episode of toothache and 1 of acne were considered unrelated.
There were no serious adverse events and no deaths. Combination therapy with
oseltamivir and rimantadine at recommended dosages in adults had no discernible
effect on the pharmacokinetics of either drug and raised no tolerability issues.
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