Publication Title: 
British Journal of Clinical Pharmacology

AIMS: To assess the haemodynamic, electrocardiographic and glycaemic effects of piperaquine-dihydroartemisinin (Artekin) fixed combination therapy in uncomplicated malaria. METHODS: Sixty-two Cambodians (32 children and 30 adults) with falciparum or vivax malaria were given Artekin given as four age-based oral doses over 32 h. Supine and erect blood pressure, the electrocardiographic QT interval and plasma glucose were measured before treatment and then at regular intervals during a 4-day admission period as part of efficacy and safety monitoring.

Karunajeewa, Harin
Lim, Chiv
Hung, Te-Yu
Ilett, Kenneth F.
Denis, Mey Bouth
Socheat, Doung
Davis, Timothy M. E.
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

Combinations are set to become the mainstay in treatment and prophylaxis of malaria due to Plasmodium falciparum. Various antimalarials have been implicated in cardiotoxicity via prolongation of the QTc interval. Atovaquone-proguanil is an effective and increasingly popular antimalarial choice when used alone or with artesunate in areas of drug resistance. We report the results of an investigation carried out on the Thai-Burmese border in 42 patients randomized to receive either atovaquone-proguanil or atovaquone-proguanil-artesunate for three days.

Gupta, Ravindra K.
van Vugt, Michèle
Paiphun, Lucy
Slight, Thra
Looareesuwan, Sornchai
White, Nicholas J.
Nosten, François
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

Patient data from eight clinical trials were pooled and analyzed to study the efficacy and safety of the six-dose versus four-dose regimen of artemether-lumefantrine (coartemether; Coartem) in children weighing 5-25 kg. A total of 544 patients with uncomplicated P. falciparum malaria (six-dose: 343; four-dose: 201), matched for demographic and baseline characteristics and individual coartemether doses were included in the analysis.

Makanga, Michael
Premji, Zul
Falade, Catherine
Karbwang, Juntra
Mueller, Edgar A.
Andriano, Kim
Hunt, Philip
de Palacios, Patricia Ibarra
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

Dihydroartemisinin-piperaquine (DP) could become a leading fixed combination malaria treatment worldwide. Although there is accumulating evidence of efficacy and safety from clinical trials, data on cardiotoxicity are limited. In two randomized controlled trials in Thailand, 56 patients had ECGs performed before treatment, 4 hours after the first dose, and 4 hours after the last dose. The mean (95% CI) changes in QTc interval (Bazett's correction) were 2 (-6 to 9) ms and 14 (7 to 21) ms, respectively.

Mytton, Oliver T.
Ashley, Elizabeth A.
Peto, Leon
Price, Ric N.
La, Yar
Hae, Rae
Singhasivanon, Pratap
White, Nicholas J.
Nosten, François
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

Several antimalarials can cause significant prolongation of the electrocardiograph QT interval, which can be associated with an increased risk of potentially lethal ventricular arrhythmias. High doses of artemether and artemotil have been associated with QT prolongation in dogs, raising the possibility of a class effect with the artemisinin derivatives. Serial electrocardiograms were recorded, and QTc interval was calculated before and after administration of artesunate by intravenous injection in patients with severe falciparum malaria in Bangladesh.

Maude, Richard J.
Plewes, Katherine
Faiz, M. Abul
Hanson, Josh
Charunwatthana, Prakaykaew
Lee, Sue J.
Tarning, Joel
Yunus, Emran Bin
Hoque, M. Gofranul
Hasan, Mahatab Uddin
Hossain, Amir
Lindegardh, Niklas
Day, Nicholas P. J.
White, Nicholas J.
Dondorp, Arjen M.
Publication Title: 
Tropical medicine & international health: TM & IH

OBJECTIVE: To ascertain whether mefloquine (MQ) produces electrocardiogram (ECG) changes that could be a risk for Torsades de Pointe (TdP), a potentially malignant, ventricular tachyarrhythmia. METHODS: We measured the Fridericia corrected QT (QTcF) intervals on 12 lead ECGs on days (D) 0, 3, 7 in Plasmodium falciparum infected adults, treated with oral artesunate (AS) and MQ as a new fixed dose (n = 25) combination or loose tablets (n = 25) over 3 days. Target total doses were 12 mg/kg of AS and 24-25 mg/kg of MQ. MQ concentrations ([MQ]) were measured by HPLC.

Krudsood, S.
Looareesuwan, S.
Wilairatama, P.
Leowattana, W.
Tangpukdee, N.
Chalermrut, K.
Ramanathan, S.
Navaratnam, V.
Olliaro, P.
Vaillant, M.
Kiechel, J. R.
Taylor, W. R. J.
Publication Title: 
Antimicrobial Agents and Chemotherapy

Artemisinin-naphthoquine (ART-NQ) is a fixed-dose coformulated antimalarial therapy recommended as a single-dose treatment and marketed in Papua New Guinea among other tropical countries. We conducted a tolerability, safety, and efficacy study of ART-NQ for Papua New Guinean children aged 5 to 12 years with uncomplicated malaria, comparing single-dose ART-NQ (15 and 6 mg/kg of body weight) given with water (group 1; n = 15), single-dose ART-NQ (22 and 9 mg/kg) given with milk (group 2; n = 17), or two daily doses of 22 and 9 mg/kg given with water (group 3; n = 16).

Benjamin, John
Moore, Brioni
Lee, Sook Ting
Senn, Michèle
Griffin, Susan
Lautu, Dulci
Salman, Sam
Siba, Peter
Mueller, Ivo
Davis, Timothy M. E.
Publication Title: 
BMJ case reports

A 40-year-old healthy manual labourer from a malaria endemic area with no known risk factors for atherosclerotic coronary vascular disease was admitted to our hospital with a history of fever with chills and rigours. Physical examination revealed tachypnoea and icterus. Peripheral smear showed trophozoites of Plasmodium vivax and thrombocytopaenia. The patient was administered artesunate. Six hours after admission, he complained of severe substernal chest pain. A 12-lead ECG revealed ST elevations in leads I, II and aVL.

Bhat, Smitha
Alva, Jayaprakash
Muralidhara, Krithika
Fahad, Sayid
Publication Title: 
Malaria Journal

BACKGROUND: Several anti-malarial drugs are associated with adverse cardiovascular effects. These effects may be exacerbated when different anti-malarials are used in combination. There has been no report yet on the potential cardiac effects of the combination artesunate-amodiaquine. METHODS: Electrocardiographic (ECG) intervals in Ghanaian children with uncomplicated malaria treated with artesunate-amodiaquine (n=47), were compared with that of children treated with artemether-lumefantrine (n=30). The ECG measurements were repeated one, two, three, seven and 28 days after treatment.

Adjei, George O.
Oduro-Boatey, Collins
Rodrigues, Onike P.
Hoegberg, Lotte C.
Alifrangis, Michael
Kurtzhals, Jorgen A.
Goka, Bamenla Q.
Publication Title: 
Malaria Journal

BACKGROUND: Human cerebral malaria (HCM) is a life-threatening complication caused by Plasmodium falciparum infection that continues to be a major global health problem despite optimal anti-malarial treatment. In the experimental model of cerebral malaria (ECM) by Plasmodium berghei ANKA, bolus administration of nimodipine at high doses together with artemether, increases survival of mice with ECM.

Martins, Yuri C.
Clemmer, Leah
Orjuela-Sánchez, Pamela
Zanini, Graziela M.
Ong, Peng Kai
Frangos, John A.
Carvalho, Leonardo J. M.


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