ArticleAntimicrobial agents and chemotherapy2009
Efficacy of the novel diamidine compound 2,5-Bis(4-amidinophenyl)- furan-bis-O-Methlylamidoxime (Pafuramidine, DB289) against Trypanosoma brucei rhodesiense infection in vervet monkeys after oral administration.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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17 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Novel amidines and analogues as promising agents against intracellular parasites: a systematic review.Parasitology · 2013Pooled it
- Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies.PLoS neglected tropical diseases · 2016Trial
- Efficacy and Safety of Pafuramidine versus Pentamidine Maleate for Treatment of First Stage Sleeping Sickness in a Randomized, Comparator-Controlled, International Phase 3 Clinical Trial.PLoS neglected tropical diseases · 2016Trial
- Induction of AML cell differentiation using HOXA9/DNA binding inhibitors as a potential therapeutic option for HOXA9-dependent AML.HemaSphere · 2024Article
- Binding to the DNA Minor Groove by Heterocyclic Dications: from AT Specific to GC Recognition Compounds.Current protocols · 2023Review
- Current Treatments to Control African Trypanosomiasis and One Health Perspective.Microorganisms · 2022Review
- New Drugs for Human African Trypanosomiasis: A Twenty First Century Success Story.Tropical medicine and infectious disease · 2020Review
- Chemotherapy of second stage human African trypanosomiasis: comparison between the parenteral diamidine DB829 and its oral prodrug DB868 in vervet monkeys.PLoS neglected tropical diseases · 2015Article
- CYP1A1 and CYP1B1-mediated biotransformation of the antitrypanosomal methamidoxime prodrug DB844 forms novel metabolites through intramolecular rearrangement.Journal of pharmaceutical sciences · 2014Article
- Safety, pharmacokinetic, and efficacy studies of oral DB868 in a first stage vervet monkey model of human African trypanosomiasis.PLoS neglected tropical diseases · 2013Article
- Binding to the DNA minor groove by heterocyclic dications: from AT-specific monomers to GC recognition with dimers.Current protocols in nucleic acid chemistry · 2012Review
- Pharmacology of DB844, an orally active aza analogue of pafuramidine, in a monkey model of second stage human African trypanosomiasis.PLoS neglected tropical diseases · 2012Article
- A semiphysiologically based pharmacokinetic modeling approach to predict the dose-exposure relationship of an antiparasitic prodrug/active metabolite pair.Drug metabolism and disposition: the biological fate of chemicals · 2012Article
- The trypanocidal activity of amidine compounds does not correlate with their binding affinity to Trypanosoma cruzi kinetoplast DNA.Antimicrobial agents and chemotherapy · 2011Article
- State of the art in African trypanosome drug discovery.Current topics in medicinal chemistry · 2011Review
- Application of monoclonal antibodies to measure metabolism of an anti-trypanosomal compound in vitro and in vivo.Journal of clinical laboratory analysis · 2010Article
- New treatment option for second-stage African sleeping sickness: in vitro and in vivo efficacy of aza analogs of DB289.Antimicrobial agents and chemotherapy · 2009Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Owing to the lack of oral drugs for human African trypanosomiasis, patients have to be hospitalized for 10 to 30 days to facilitate treatment with parenterally administered medicines. The efficacy of a novel orally administered prodrug, 2,5-bis(4-amidinophenyl)-furan-bis-O-methlylamidoxime (pafuramidine, DB289), was tested in the vervet monkey (Chlorocebus [Cercopithecus] aethiops) model of sleeping sickness. Five groups of three animals each were infected intravenously with 10(4) Trypanosoma brucei rhodesiense KETRI 2537 cells. On the seventh day postinfection (p.i.) in an early-stage infection, animals in groups 1, 2, and 3 were treated orally with pafuramidine at dose rates of 1, 3, or 10 mg/kg of body weight, respectively, for five consecutive days. The animals in groups 4 and 5 were treated with 10 mg/kg for 10 consecutive days starting on the 14th day p.i. (group 4) or on the 28th day p.i. (group 5), when these animals were in the late stage of the disease. In the groups treated in the early stage, 10 mg/kg of pafuramidine completely cured all three monkeys, whereas lower doses of 3 mg/kg and 1 mg/kg cured only one of three and zero of three monkeys, respectively. Treatment of late-stage infections resulted in cure rates of one of three (group 4) and zero of three (group 5) monkeys. These studies demonstrated that pafuramidine was orally active in monkeys with early-stage T. brucei rhodesiense infections at dose rates above 3 mg/kg for 5 days. It was also evident that the drug attained only minimal efficacy against late-stage infections, indicating the limited ability of the molecule to cross the blood-brain barrier. This study has shown that oral diamidines have potential for the treatment of early-stage sleeping sickness.
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