Uses
Rimantadine act by blocking the M2 ion channel which is required for uptake of protons into the interior of the virus to permit acid-promoted viral uncoating (decapsidation).
Definition
ChEBI: 1-(1-adamantyl)ethanamine is an alkylamine.
Brand name
Flumadine (Forest).
General Description
Resistant variants of influenza type A have been recoveredfrom rimantadine-treated patients.Resistance with inhibitory concentrations increased morethan 100-fold have been associated with single nucleotidechanges that lead to amino acid substitutions in the transmembranedomain of M2. rimantadineshare cross-susceptibility and resistance.
Pharmaceutical Applications
An analog of amantadine, supplied as the hydrochloride for
oral administration.
Mechanism of action
Rimantadine hydrochloride (α-methyl-1-adamantanemethylamine hydrochloride) is a synthetic adamatane
derivative that is structurally and pharmacologically related to amantadine. It appears to be more
effective than amantadine hydrochloride against influenza A, with fewer CNS side effects. Rimantadine
hydrochloride is thought to interfere with virus uncoating by inhibiting the release of specific proteins. It
may act by inhibiting RT or the synthesis of virus-specific RNA, but it does not inhibit virus adsorption or
penetration. It appears to produce a virustatic effect early in the virus replication. It is used widely in
Russia and Europe.
Pharmacokinetics
Oral absorption: >90%
Cmax 100 mg oral (every 12 h): 0.4–0.5 mg/L after 2–6 h
Plasma half-life: c. 35 h
Volume of distribution: Very large
Plasma protein binding: c. 40%
Absorption and distribution
Single- and multiple-dose pharmacokinetic studies in elderly patients and young adults are remarkably similar. The steadystate concentration in nasal mucus develops by day 5 at a concentration approximately 1.5-fold higher than plasma.
Metabolism
In contrast to amantadine, rimantadine is extensively metabolized in the liver by hydroxylation and glucuronidation.
Excretion
Less than 20% is excreted unchanged in the urine and most of the breakdown products are excreted by this route. Thus, the plasma half-life is much less affected by renal dysfunction than that of amantadine.
Clinical Use
Prophylaxis and treatment of influenza A H1N1 infections
Since prolonged administration is well tolerated by elderly
patients, the drug is preferable to amantadine.
Clinical Use
rimantadine is used for the treatment
of diseases caused by influenza A strains.
Side effects
Rimantadine has significantly fewer side effects than amantadine
at equivalent doses, perhaps because of differences
in pharmacokinetics, since with equal doses the blood levels
are considerably lower. CNS side effects are not significantly
higher than placebo.
