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Pharmacokinetics and Safety of Coadministered Oseltamivir and Rimantadine in Healthy Volunteers: An Open‐Label, Multiple‐Dose, Randomized, Crossover Study
Author(s) -
CirrincioneDall Georgina,
Brennan Barbara J.,
BallesterSanchis Rosa M.,
Navarro Mercidita T.,
Davies Brian E.
Publication year - 2012
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 - 10.1177/0091270011412960
Subject(s) - tolerability , medicine , rimantadine , pharmacokinetics , pharmacology , neuraminidase inhibitor , crossover study , adverse effect , oseltamivir , bioequivalence , combination therapy , randomized controlled trial , influenza a virus , placebo , immunology , covid-19 , virus , alternative medicine , disease , pathology , infectious disease (medical specialty)
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.