1-AdaMantanethylaMine

Использование

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).

Общее описание

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.

Фармацевтические приложения

An analog of amantadine, supplied as the hydrochloride for oral administration.

Механизм действия

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.

Фармакокине?тика

Oral absorption: >90%
C_max 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.

Клиническое использование

Prophylaxis and treatment of influenza A H1N1 infections Since prolonged administration is well tolerated by elderly patients, the drug is preferable to amantadine.

Побочные эффекты

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.