Randomized Comparison of Artemether-Benflumetol and Artesunate-Mefloquine in Treatment of MultidrugResistant Falciparum Malaria

Vugt, Michèle van; Brockman, Alan; Gemperli, B; Luxemburger, Christine; Gathmann, Insa; Royce, Catherine; Slight, Thra; Looareesuwan, S; White, Nicholas J.; Nosten, François

doi:10.1128/aac.42.1.135

Cited by 149 publications

(65 citation statements)

References 17 publications

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“…Unfortunately, halofantrine was found to prolong the QT interval and thus its use is now limited [32]. The most recent amino alcohol, lumefantrine was developed by the Chinese [54] and resembles halofantrine in having a very lipophilic, electron-deficient tricyclic conjugated system. Lumefantrine has solubility-limited oral bioavailability, making the successful combination with artemether a twice daily drug [10].…”

Section: Amino Alcohols -The Next Generationmentioning

confidence: 99%

The State of the Art in Anti-Malarial Drug Discovery and Development

Burrows

Chibale²,

Wells

2011

CTMC

144

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Malaria is one of the most prevalent and devastating infectious diseases of our time. Yet, unfortunately, apart from artemisinin combination therapies there are relatively few effective treatments for Plasmodium falciparum and only one treatment for the radical cure of Plasmodium vivax. Novel classes of antimalarial medicines are urgently needed given the long-term inevitability of resistance to current therapies and the need for drugs that are well tolerated by all. This review summarises the antimalarials developed and registered thus far, as well as describing some of the new small molecule therapy approaches being developed as a contribution towards the malaria eradication agenda.

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Section: Amino Alcohols -The Next Generationmentioning

confidence: 99%

The State of the Art in Anti-Malarial Drug Discovery and Development

Burrows

Chibale²,

Wells

2011

CTMC

144

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“…Unfortunately, there is a lack of pharmacokinetic information about DBB although it is considered a putative -albeit hitherto elusivemetabolite of lumefantrine. As lumefantrine is tolerated well in therapeutic doses [17][18][19][20], it may be expected that the same will hold for DBB. Recent hERG channel studies with DBB indicate better cardio-tolerability as compared to chloroquine and mefloquine [21].…”

Section: Discussionmentioning

confidence: 98%

Synergismus zwischen Desbutyl-Benflumetol und Retinol bei Plasmodium falciparum in vitro

Samal

Rojanawatsirivet

Wernsdorfer

et al. 2005

Wien Klin Wochenschr

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This in vitro study was conducted to assess the blood schizontocidal activity of desbutyl-benflumetol (DBB), a new benzindene derivative, retinol and a combination of both compounds. The tests were carried out according to the methodology of the WHO standard test Mark II, measuring the drug-dependent inhibition of schizont maturation, and using 43 fresh isolates of Plasmodium falciparum from northwestern Thailand, an area with established multidrug-resistance. DBB and retinol showed a mean 50% effective concentration (EC-50) of 3.73 nM and 466.86 nM and 90% effective concentration (EC-90) of 19.83 nM and 5531.69 nM respectively. The combination of DBB and 3.50 muM retinol showed strong inhibition of schizont maturation, with an EC-90 for DBB of 0.67 nM. At the therapeutically relevant EC-99, the combination was about 10 times more effective than expected, suggesting that retinol potentiated the effect of DBB. A concentration of 3.50 muM retinol corresponds to the 95th percentile of the physiological serum levels. It is well known that retinol levels are significantly decreased in acute falciparum malaria. Supplementation with retinol during malaria treatment may improve the therapeutic results of blood schizontocides of the fluorene class.

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“…The most often used free combinations are artesunate/mefloquine (Artequin) [72,85], artesunate/amodiaquine (Arsucam) [86], artesunate/ sulfadioxine/pyrimethamine (Arsudar) [87], artesunate/ malarone. Efficient fixed combinations are artemether/ lumefantrine (Riamet and Coartem) [88][89][90], dihydroartemisinin-piperaquine (Artekin), artesunate/Lapdap [67].…”

Section: Artemisinin Derivativesmentioning

confidence: 99%

Quinolone-Based Drugs Against Toxoplasma gondii and Plasmodium spp

Anquetin

Greiner²,

Vierling³

2005

CDTID

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Owing to the rapid emergence of multi-resistant strains of Plasmodium spp. (the causative agents of malaria) and the limitations of drugs used against Toxoplasma gondii (an important opportunistic pathogen associated with AIDS and congenital birth defects), the discovery of new therapeutical targets and the development of new drugs are needed. The presence of the prokaryotic-like organelle in apicomplexan parasites (i.e. plastids), which comprise these major human pathogens, may represent a unique target for antibiotics against these protozoa. Quinolones which are known to be highly potent against bacteria were also found to specifically disrupt these parasites. They inhibit DNA replication by interacting with two essential bacterial type II topoisomerases, DNA gyrase and topoisomerase IV. There are some clues that quinolones act on plastids with a similar mechanism of action. After a brief presentation of plasmodium and toxoplasma dedicated to their life cycle, the chemotherapies presently used in clinics to fight against these protozoa and the potential new targets and drugs, we will focus our attention on their plastid which is one of these promising new targets. Then, we will present the various drugs and generations of quinolones, the leading molecules, and their inhibitory effects against these parasites together with their pharmacological properties that have been established from in vitro and in vivo studies. We will also discuss their possible mode of action.

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Randomized Comparison of Artemether-Benflumetol and Artesunate-Mefloquine in Treatment of MultidrugResistant Falciparum Malaria

Cited by 149 publications

References 17 publications

The State of the Art in Anti-Malarial Drug Discovery and Development

The State of the Art in Anti-Malarial Drug Discovery and Development

Synergismus zwischen Desbutyl-Benflumetol und Retinol bei Plasmodium falciparum in vitro

Quinolone-Based Drugs Against Toxoplasma gondii and Plasmodium spp

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