OXAMNIQUINE(200MG)DISCONTINUED

Описание

Oxamniquine was originally investigated in the 1960s and was found to have limited antiprotozoal activity, with activity against Schi stosoma mansoni but no activity against the other two schistosomal organisms. In addition, the drug is stage specific, with activity against cercariae and very young schistosomula and adult worms. For reasons that remain unknown, the drug is more effective against adult male worms than against female worms. The drug has structural similarity to hycanthone, which is no longer used because of severe toxicity and teratogenic effects.

Использование

Antischistosomal.

Определение

ChEBI: A member of the class of quinolines that is 1,2,3,4-tetrahydroquinoline which is substituted at positions 2, 6, and 7 by (isopropylamino)methyl, hydroxymethyl, and nitro groups, respectively.

Показания

Oxamniquine (Vansil) is a tetrahydroquinoline that stimulates parasite muscular activity at low concentrations but causes paralysis at higher concentrations. The drug may act by esterification and binding of DNA, leading to the death of the schistosome by interruption of its nucleic acid and protein synthesis. The fluke may esterify oxamniquine to produce a reactive metabolite that alkylates parasite DNA. Resistance results from absent or defective esterifying activity of the drug. Oxamniquine has a restricted range of efficacy, being active only against S. mansoni infections.
Oxamniquine is given orally and is readily absorbed from the intestinal tract. Peak concentrations in plasma are obtained in about 3 hours. The drug is excreted in urine mostly as a 6-carboxyl derivative.
Side effects include CNS toxicity with unsteadiness and occasionally seizures, especially in patients with a history of seizures. It is contraindicated in pregnancy.

Антимикробная активность

Activity is restricted to Schistosoma mansoni. Some strains, particularly those in Egypt and Southern Africa, require higher doses for efficacy owing to innate tolerance.

Фармацевтические приложения

A synthetic quinolinemethanol, available for oral administration.

Механизм действия

Oxamniquine is activated via esterification to a biological ester that spontaneously dissociates to an electrophile, which alkylates the helminth DNA, leading to irreversible inhibition of nucleic acid metabolism. Resistant helminths do not esterify oxamniquine; therefore, activation does not occur. Other metabolic reactions consist of oxidative reactions, leading to inactivation. The metabolites are excreted primarily in the urine.

Фармакокине?тика

It is rapidly absorbed after oral administration, achieving a peak concentration of 0.3–2.5 mg/L 1–3 h after an oral dose of 15 mg/kg body weight. Peak levels following intramuscular treatment at 7.5 mg/kg generally do not exceed 0.15 mg/L. It is extensively metabolized to biologically inactive 6-carboxylic and 2-carboxylic acid derivatives, which are excreted in the urine, mostly within 12 h.

Клиническое использование

Infection with S. mansoni

Побочные эффекты

Dizziness, sleepiness, nausea and headache occur frequently. Other side effects are probably due to the death and disintegration of the worms in the liver. Following treatment, urine may become red.

Профиль безопасности

Poison by ingestion, intraperitoneal and intramuscular routes. Human mutation data reported. An antischistosomal agent. When heated to decomposition it emits toxic fumes of NOx.