Amantadine
Approximately 90% of amantadine is excreted unchanged in the urine by glomerular filtration and tubular secretion. Thus, renal clearance of amantadine is reduced substantially among persons with renal insufficiency, and dosages might need to be decreased (see Dosage).
Rimantadine
Approximately 75% of rimantadine is metabolized by the liver. The safety and pharmacokinetics of rimantadine among persons with liver disease have been evaluated only after single-dose administration. In a study of persons with chronic liver disease (the majority with stabilized cirrhosis), no alterations in liver function were observed after a single dose. However, for persons with severe liver dysfunction, the apparent clearance of rimantadine was 50% lower than that reported for persons without liver disease.
Rimantadine and its metabolites are excreted by the kidneys. The safety and pharmacokinetics of rimantadine among patients with renal insufficiency have been evaluated only after single-dose administration. Further studies are needed to determine multiple-dose pharmacokinetics and the most appropriate dosages for patients with renal insufficiency. In a single-dose study of patients with anuric renal failure, the apparent clearance of rimantadine was approximately 40% lower, and the elimination half-life was approximately 1.6-fold greater than that among healthy persons of the same age. Hemodialysis did not contribute to drug clearance. In studies of persons with less severe renal disease, drug clearance was also reduced, and plasma concentrations were higher than those among control patients without renal disease who were the same weight, age, and sex.
Zanamivir
In studies of healthy volunteers, approximately 7%–21% of the orally inhaled zanamivir dose reached the lungs, and 70%–87% was deposited in the oropharynx. Approximately 4%–17% of the total amount of orally inhaled zanamivir is systemically absorbed. Systemically absorbed zanamivir has a half-life of 2.5–5.1 hours and is excreted unchanged in the urine. Unabsorbed drug is excreted in the feces.
Oseltamivir
Approximately 80% of orally administered oseltamivir is absorbed systemically. Absorbed oseltamivir is metabolized to oseltamivir carboxylate, the active neuraminidase inhibitor, primarily by hepatic esterases. Oseltamivir carboxylate has a half-life of 6–10 hours and is excreted in the urine by glomerular filtration and tubular secretion via the anionic pathway. Unmetabolized oseltamivir also is excreted in the urine by glomerular filtration and tubular secretion.
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