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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.
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Antiprotozoal (Trypanosoma). Showing anti-Trypanosoma cruzi activity.
Indications
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.
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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.
Pharmaceutical Applications
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.
Mechanism of action
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.
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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.
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