Coartemether (artemether and lumefantrine): an oral antimalarial drug

Wernsdorfer, Walther H.

doi:10.1586/14787210.2.2.181

Cited by 56 publications

(29 citation statements)

References 46 publications

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“…Unfortunately, to date little has been completed on the praeclinical and clinical development of DBB as an antimalarial drug. DBB was long considered to be a metabolite of lumefantrine, but there is until now no evidence that lumefantrine is metabolically converted to DBB in human subjects [11]. Recent hERG K + studies classified DBB as less inhibitory compared to mefloquine and quinine [12].…”

Section: Discussionmentioning

confidence: 99%

In vitro interaction between artemisinin and chloroquine as well as desbutyl-benflumetol in Plasmodium vivax

Kyavar

Rojanawatsirivet

Kollaritsch

et al. 2006

Wien Klin Wochenschr

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Malaria resulting from infection with Plasmodium vivax rarely causes death, however, patients usually suffer acute debilitating clinical symptoms and the recovery is slow. This study had the objective of assessing the pharmacodynamic interaction between artimisinin and chloroquine with a view of a potential acceleration of the clinicalparasitological response, and the investigation of therapeutic alternatives in the event of chloroquine resistance in Plasmodium vivax. Tests were based on the growth inhibition of Plasmodium vivax, determined by morphological differential counts of 200 asexual parasites. In total 45 isolates were evaluated successfully with parallel tests for artemisinin, chloroquine and desbutylbenflumetol (DBB) alone and combinations of artemisinin + chloroquine and artemisinin + DBB. Total inhibition was reached at a mean concentration of 1274.8 nM (95% CI 898.5 to 1808.7 nM), and 1852.2 nM (95% CI 1539.5 to 2228.6 nM) for artemisinin, and chloroquine respectively, whilst the 1:1 (m/m) combination of artemisinin and chloroquine was 1860.2 nM (95% CI 1454.4 to 2379.3 nM). EC(50) and EC(90) were 129.9 nM and 1058.5 nM for chloroquine, 32.6 nM and 735.5 nM for artemisinin, and 73.6 nM and 1103.0 nM for the 1:1 combination of both drugs. Interaction analysis according to Berenbaum yielded for the artemisinin + chloroquine combination at the EC(50) a mean SigmaFIC of 1.1126, at the EC(90) a mean SigmaFIC of 1.0331, and at the EC(99) a mean SigmaFIC of 1.1857. These results revealed marked additive interaction. For desbutylbenflumetol (DBB) the EC(50) and EC(90) were 1.5 nM and 28.8 nM, complete growth inhibition was observed at 90.4 nM (95% CI 75.1 to 108.7 nM). Interaction analysis indicated moderate antagonism at the lower concentration ranges, at the EC(90) additive interaction with a mean SigmaFIC of 1.0300, and synergism at the therapeutically most important EC(99) with a mean SigmaFIC of 0.5990.

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Section: Discussionmentioning

confidence: 99%

In vitro interaction between artemisinin and chloroquine as well as desbutyl-benflumetol in Plasmodium vivax

Kyavar

Rojanawatsirivet

Kollaritsch

et al. 2006

Wien Klin Wochenschr

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“…Although we did not measure this factor in Mbarara, African isolates have considerably lower IC50 values than those from western Thailand, where the high IC50 values are probably explained by the in-vitro cross-resistance between lumefantrine and mefloquine and halofantrine. 31,33,34 A day-7 lumefantrine concentration of less than 280 g/L as a pharmacokinetic predictor that treatment will not work might not be applicable to all regions, and further research should be done to assess the appropriate threshold as a function of parasite sensitivity.…”

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confidence: 99%

Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial

Piola¹,

Fogg²,

et al. 2005

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CitationSupervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial., 365 (9469 Articles IntroductionWith an estimated 500 million individuals affected every year, malaria is a leading cause of morbidity and mortality in sub-Saharan Africa along with HIV/AIDS. 1Of the 1 million deaths caused by malaria worldwide, about 90% occur in African children, a situation compounded by the emergence of drug resistance. 2In Uganda, which had a population of 24·7 million in 2003, an estimated 9·8 million individuals are infected with malaria every year (John Bosco Rwakimari, Ugandan Ministry of Health, Uganda, personal communication; http://www.health.go.ug). To tackle malaria-related mortality and morbidity, the Ugandan Ministry of Health (MoH) is concentrating on early diagnosis and effective treatment of the disease. In the 1970s and the 1980s, high malaria awareness in the population and easy access to cheap and effective antimalarials such as chloroquine and sulfadoxinepyrimethamine ensured the disease was reasonably well controlled. However, resistance to these drugs is now widespread in Uganda and in other parts of east Africa, with adverse consequences for malaria control. 3-7The MoH-recommended first-line antimalarial drug in Uganda is chloroquine combined with sulfadoxinepyrimethamine, 6 though introduction of artemisininbased combination treatments (ACTs) is planned for 2005.8 Day-28 cure rates of 52%, 9 65%, 7 and 77% 10 have been reported for this combination in different parts of Uganda. ACTs are judged effective in Africa, where they improve cure rates and reduce gametocyte carriage compared with presently used monotherapies.11,12 To combat drug-resistant malaria in Africa, WHO advocates the adoption of ACTs as first-line treatment.2 The use of the non-ACT combination of amodiaquine and sulfadoxine-pyrimethamine is considered by some as an interim measure while waiting for ACTs to become widely available. Day-28 efficacy rates of this combination were 84% and 90% in two studies in Uganda. 7,9 Artemether-lumefantrine (Coartem, Novartis Pharma, Basel, Switzerland) is the only fixed-dose formulation ACT on the WHO essential drug list. However, the combination is not registered for use in pregnant women, and was not registered for children under 10 kg in weight when we did our trial. Results of studies [13][14][15] from southeast Asia show that the six-dose regimen of artemether-lumefantrine has cure rates of more than 96%, is well tolerated, and has a good safety profile when Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial Patrice Piola, Carole Fogg, Francis Bajunirwe, Samuel Biraro, Francesco Grandesso, Eugene Ruzagira, Joseph Babigumira, Isaac Kigozi, James Kiguli, Juliet Kyomuhendo, Laurent Ferradini, Walter Taylor, Francesco Checchi, Jean-Paul Guthmann S...

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“…Artemether/lumefantrine should be administered with fatty food to obtain optimal plasma drug concentrations [20]. Dihydroartemisinin/piperaquine, in contrast, should be taken fasting.…”

Section: Tricky Treatmentsmentioning

confidence: 99%

Current Challenges in Travelers’ Malaria

Schlagenhauf

Petersen

2013

Curr Infect Dis Rep

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Travel health providers are often confronted with complex scenarios when advising travelers on malaria prevention. Current challenges in prevention include malaria risk assessment, where a detailed itinerary and knowledge of malaria epidemiology are needed. Up-to-date information on the correct use, limitations, and drug interactions of current priority chemoprophylaxis agents (atovaquone/proguanil, mefloquine, doxycycline) is key. Another challenge is to identify and reach travelers who are most at risk of malaria, such as the traveler visiting friends and relatives. Posttravel, delays in presentation, diagnosis, and inappropriate treatment of malaria are key risk factors leading to death. Treatment of malaria is an emergency requiring expert in-patient management and referral to a center with adequate expertise. Artemisinin combination therapies are the drugs of choice for uncomplicated malaria. Complicated malaria is treated preferably with intravenous artesunate, and the supply and quality of this life-saving antimalarial in some settings can pose one of the most urgent challenges in travelers' malaria. Abstract Travel health providers are often confronted with complex scenarios when advising travelers on malaria prevention. Current challenges in prevention include malaria risk assessment, where a detailed itinerary and knowledge of malaria epidemiology are needed. Up-to-date information on the correct use, limitations, and drug interactions of current priority chemoprophylaxis agents (atovaquone/proguanil, mefloquine, doxycycline) is key. Another challenge is to identify and reach travelers who are most at risk of malaria, such as the traveler visiting friends and relatives. Posttravel, delays in presentation, diagnosis, and inappropriate treatment of malaria are key risk factors leading to death. Treatment of malaria is an emergency requiring expert in-patient management and referral to a center with adequate expertise. Artemisinin combination therapies are the drugs of choice for uncomplicated malaria. Complicated malaria is treated preferably with intravenous artesunate, and the supply and quality of this life-saving antimalarial in some settings can pose one of the most urgent challenges in travelers' malaria.

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Coartemether (artemether and lumefantrine): an oral antimalarial drug

Cited by 56 publications

References 46 publications

In vitro interaction between artemisinin and chloroquine as well as desbutyl-benflumetol in Plasmodium vivax

In vitro interaction between artemisinin and chloroquine as well as desbutyl-benflumetol in Plasmodium vivax

Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial

Current Challenges in Travelers’ Malaria

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