Нифуртимокс

Описание

Nifurtimox is manufactured by Bayer and marketed under the trade name Lampits.It is a nitrofuran derivative that was developed specifically for the treatment of American trypanosomiasis (Chagas'disease) (Packachanian, 1957). Nifurtimox is one of two drugs approved for use in treatment of Chagasdisease. It was shown to be the most active and least toxic of this group of agents in preclinical studies and was evaluated in clinical trials in the 1960s and subsequently marketed for use in Chagas’ disease in Latin America in the late 1960s and early 1970s. Although the use of nifurtimox for Chagas’ disease has decreased with the availability of benznidazole, a potentially more active and less toxic agent, there has been a resurgence of interest in and use of nifurtimox for the treatment of second-stage human African trypanosomiasis (HAT)caused by Trypanosoma brucei gambiense.

Химические свойства

Orange Solid

Использование

Antiprotozoal (Trypanosoma). Showing anti-Trypanosoma cruzi activity.

Показания

Nifurtimox (Lampit) is a nitrofuran derivative whose likely mechanism of action for killing of trypanosomes is through the production of activated forms of oxygen. Nifurtimox is reduced to the nitro anion radical, which reacts with oxygen to produce superoxide and hydrogen peroxide. The free radical metabolites, an absence of parasite catalase, and a peroxide deficiency lead to lipid peroxidation and cell damage. This production of activated oxygen results in toxicity to the protozoal cells.

Общее описание

Nifurtimox acts as a hypoxia-activated cytotoxin, which specifically kills clonogenic tumor cells under hypoxic conditions. It is used to treat Chagas disease and African trypanosomiasis. Nifurtimox inhibits neuroblastoma and medulloblastoma cell growth.

Фармацевтические приложения

A water-soluble synthetic compound available for oral use. It exhibits antibacterial activity typical of the group, but its most notable property is its activity against trypanosomes, especially Trypanosoma cruzi.
A plasma concentration of 0.5–1 mg/L is achieved c. 2 h after an oral dose of 15 mg/kg. The plasma half-life is 2–4 h. In common with other nitrofurans, it is rapidly and extensively metabolized, so that less than 1% of a dose is excreted intact in the urine. In renal failure, clearance is somewhat reduced but the half-life is unchanged.
Adverse events are common. Many patients experience anorexia, which may be combined with vomiting and abdominal pain. There may also be neurological reactions such as restlessness, insomnia, headache and disorientation.
It is used in the treatment of Chagas disease (South American trypanosomiasis). It has also found some use in the treatment of African sleeping sickness in combination with eflornithine.

Механизм действия

The drug is given orally and is well absorbed from the gastrointestinal tract. It is rapidly metabolized, and only low levels are found in blood and tissues.The drug is excreted in the urine, primarily in the form of metabolites.

Побочные эффекты

Although side effects occur in approximately half the patients treated with nifurtimox, it is necessary to discontinue treatment in only a minority. Nausea, vomiting, abdominal pain, skin rashes, headache, insomnia, convulsions, and myalgia all have been reported.