Efficacy of artemether in severe falciparum malaria in African children

Sowunmi, A.; Oduola, A. M. J.

doi:10.1016/0001-706x(95)00143-3

Cited by 20 publications

(7 citation statements)

References 12 publications

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“…Bradycardia was observed as an adverse event in 1.1% of patients receiving PA and 0.8% with AL. However, the finding of bradycardia in a young and otherwise fit population is likely to be associated with the resolution of the tachycardia associated with fever as decreases in mean heart rate were noted across all treatment groups and have been observed in other studies of anti-malarial therapy as patients become afebrile and they return to their normal baseline heart rate [33,50-52]. …”

Section: Discussionmentioning

confidence: 80%

Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials

Duparc

Borghini-Fuhrer

Craft

et al. 2013

Malar J

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BackgroundPyronaridine-artesunate (PA) is indicated for the treatment of acute uncomplicated Plasmodium falciparum and Plasmodium vivax malaria.MethodsIndividual patient data on safety outcomes were integrated from six randomized clinical trials conducted in Africa and Asia in patients with microscopically confirmed P. falciparum (five studies) or P. vivax (one study) malaria. Efficacy against P. falciparum was evaluated across three Phase III clinical trials.ResultsThe safety population included 2,815 patients randomized to PA, 1,254 to comparators: mefloquine + artesunate (MQ + AS), artemether-lumefantrine (AL), or chloroquine. All treatments were generally well tolerated. Adverse events occurred in 57.2% (1,611/2,815) of patients with PA versus 51.5% (646/1,254) for comparators, most commonly (PA; comparators): headache (10.6%; 9.9%), cough (5.9%; 5.6%) and anaemia (4.5%; 2.9%). Serious averse events were uncommon for all treatments (0–0.7%). Transient increases in alanine aminotransferase and aspartate aminotransferase were observed with PA but did not lead to any clinical sequelae. For P. falciparum malaria, day-28 PCR-corrected adequate clinical and parasitological response with PA was 93.6% ([1,921/2,052] 95% CI 92.6, 94.7) in the intent-to-treat population and 98.5% ([1,852/1,880] 95% CI 98.0, 99.1) in the per-protocol population. Median parasite clearance time was 24.1 h with PA, 31.9 h with MQ + AS, and 24.0 h with AL. Median fever clearance time was 15.5 h with PA, 15.8 h with MQ + AS, and 14.0 h with AL. By day 42, P. falciparum gametocytes had declined to near zero for all treatments.ConclusionsPyronaridine-artesunate was well tolerated with no safety concerns with the exception of mostly mild transient rises in transaminases. Efficacy was high and met the requirements for use as first-line therapy. Pyronaridine-artesunate should be considered for inclusion in malaria treatment programmes.Trial registrationClinicaltrials.gov: NCT00331136; NCT00403260; NCT00422084; NCT00440999; NCT00541385; NCT01594931

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Section: Discussionmentioning

confidence: 80%

Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials

Duparc

Borghini-Fuhrer

Craft

et al. 2013

Malar J

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“…The rates of recrudescence, fever, and parasite clearances are traditional parameters for the efficacy of the antimalarial drugs in humans. These parameters exhibit the therapeutic potential of intramuscular arteether (AE) with sesame oil (Artemotil), which has much less efficacy [3,4] compared to that of intramuscular artemether (AM) [5][6][7][8][9][10][11][12][13], oral and intravenous artesunate (AS) [2,14], and the oral dihydroartemisinin (DHA) [15][16][17][18] or even than that of intramuscular / -arteether formulated with peanut oil [19][20][21][22] in India. It is clear that the efficacy and recrudescence in humans are dissimilar along those clinical trials with different artemisinin drugs by the monotherapy.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Profiles of Rapid-Acting Artemisinins in the Antimalarial Therapy

Li¹,

Weina²,

Milhous³

2007

CDTH

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Artemisinin and its derivatives were discovered to be highly effective antimalarial drugs, which combine potent, rapid antimalarial activity with a wide therapeutic index and an absence of clinically important resistance. Artemisinins as a group are poorly efficacious at curing malaria as monotherapy. However, this shortfall is being overcome by using oral artemisinin-based combination therapy (ACT) and intravenous artesunate (AS) in sequential administration with slower acting antimalarial drugs. Pharmacokinetic and pharmacodynamic (PK/PD) evaluations demonstrate that the rapid efficacy of artemisinins is principally due to the drug peak concentration (C max ), and other pharmacokinetic parameters, such as drug exposure level (AUC) and drug exposure time (half-life) tend to be of minor significance. The evaluation also demonstrated that AS is a superior in PK/PD achievements either following oral or intravenous administration when compared to other four artemisinin drugs. Most recently, a decrease in mortality (34.7%) has been demonstrated in a large study using intravenous AS, as opposed to the standard of care quinine injection. The fast efficacy and less mortality show that current artemisinins have great advantage over other antimalarials in ACTs for uncomplicated malaria and in sequential therapy of AS injection for severe and complicated malaria.

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“…However, carbachol failed to influence action potential amplitude (APA), resting membrane potential (RMP), and maximum rate of rise of action potential upstroke (V max ). Artemisinin (1 to 100 µM) partially reversed the shortening of APD 20 , APD 50 , and APD 90 induced by carbachol in a concentration-dependent manner. Artemisinin had no influence on APA, RMP, or V max .…”

Section: Patch Clamp Studiesmentioning

confidence: 91%

“…Artemisinin is a unique type of antimalarial drug originating from a Chinese medicinal plant and has minimal adverse effects in humans [2]. According to many clinical reports, artemisinin and its derivatives are very effective against severe or complicated malarias and produce no major side effects [8,20,22,23]. Nevertheless, there is growing concern regarding the cardiac toxicity of antimalarial drugs [3,6,19,21].…”

mentioning

confidence: 99%

Anticholinergic Effects of Artemisinin, an Antimalarial Drug, in Isolated Guinea Pig Heart Preparations

Hara

Yamawaki

Shimada

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. Concern has been growing about the cardiac toxicity of antimalarial drugs. Artemisinin, a unique type of antimalarial drug originating from a Chinese medicinal plant, has minimal adverse effects, but it has been reported to inhibit delayed rectifier potassium current, a voltage-gated potassium current. However, no studies have been published concerning the effect of artemisinin on ligand-gated potassium currents. Therefore, in the present study, we examined the influence of artemisinin on the acetylcholine receptor-operated potassium current (I K.ACh ), a ligand-gated potassium current, in guinea pig atrial myocytes using a patch clamp technique. Artemisinin(1 to 300 µM) inhibited I K.ACh induced by extracellular application of both carbachol (1 µM) and adenosine (10 µM) and that induced by intracellular loading of GTPγS (100 µM) in a concentration-dependent manner. Artemisinin inhibited carbachol-induced, adenosineinduced, and GTPγS-activated I K.ACh within almost the same concentration range. In left atria, artemisinin (1 to 100 µM) partially reversed the shortening of action potential duration induced by carbachol in a concentration-dependent manner. Carbachol-induced negative inotropic action in left atria was also inhibited by artemisinin (10 to 300 µM). In conclusion, we suggest that the anticholinergic action of artemisinin is mediated through inhibition of I K.ACh via inhibition of the muscarinic potassium channel and/or associated GTPbinding proteins. KEY WORDS: acetylcholine receptor-operated potassium current, anticholinergic effect, artemisinin, guinea pig, heart muscle.

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Efficacy of artemether in severe falciparum malaria in African children

Cited by 20 publications

References 12 publications

Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials

Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials

Pharmacokinetic and Pharmacodynamic Profiles of Rapid-Acting Artemisinins in the Antimalarial Therapy

Anticholinergic Effects of Artemisinin, an Antimalarial Drug, in Isolated Guinea Pig Heart Preparations

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