Clinical trials of artemisinin and its derivatives in the treatment of malaria in China

Li, Guoqiao; Guo, Xiuping; Fu, Lin-Chun; Jian, Huaxiang; Wang, Xinhua

doi:10.1016/0035-9203(94)90460-x

Cited by 116 publications

(71 citation statements)

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“…The mechanism of action of artemisinins remains controversial [2,3] but they retain activity against parasites that have become resistant to anti-malarials such as such as chloroquine and pyrimethamine [4]. Furthermore, artemisinins can be faster acting than other drugs malarial treatments [5,6]. These impressive qualities have resulted in the World Health Organisation recommending that all anti-malarials be combined with an ART component when used in first line treatment [7].…”

Section: Artemisinin (Art) Is a Natural Trioxane That Is Isolated Fromentioning

confidence: 99%

In vitro study of the anti-cancer effects of artemisone alone or in combination with other chemotherapeutic agents

Gravett

Liu

Krishna

et al. 2010

Cancer Chemother Pharmacol

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Section: Artemisinin (Art) Is a Natural Trioxane That Is Isolated Fromentioning

confidence: 99%

In vitro study of the anti-cancer effects of artemisone alone or in combination with other chemotherapeutic agents

Gravett

Liu

Krishna

et al. 2010

Cancer Chemother Pharmacol

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“…5,6 When used alone recrudescence rates on the order of 10-20% have been reported, which may be attributable to the relatively short half-life of the compound. 7,8 Mefloquine was introduced in the 1980s and remains effective in most endemic areas for both treatment and prophylaxis of malaria. The drug is generally well tolerated, but may be occasionally associated with neuropsychiatric adverse effects.…”

Section: Introductionmentioning

confidence: 99%

Artesunate and mefloquine given simultaneously for three days via a prepacked blister is equally effective and tolerated as a standard sequential treatment of uncomplicated acute Plasmodium falciparum malaria: randomized, double-blind study in Thailand.

Krudsood¹,

Looareesuwan²,

Silachamroon³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. The combination of artesunate and mefloquine is currently one of the most effective treatments against multidrug-resistant Plasmodium falciparum malaria. To improve patient compliance to such a combination, the two agents have been combined in a prepacked single blister. Patients were instructed to simultaneously co-administer the drugs once a day for three days. In the present randomized, double-blind, parallel group, comparative, single center study in Thailand, this concept was investigated in 204 adults and children with acute, uncomplicated P. falciparum malaria. Patients were randomized into two treatment groups and received once a day over a three-day period the following: Group A received artesunate, 4-5 mg/kg/day, and mefloquine, total dose ‫ס‬ 25 mg/kg, ∼8.5 mg/kg/day, simultaneously. Group B received artesunate, 4-5 mg/kg/day, and mefloquine, total dose ‫ס‬ 25 mg/kg, sequentially (i.e., no mefloquine dose on the first day, 15 mg/kg on the second day, and 10 mg/kg on the third day). Both treatment groups showed no relevant differences in baseline demographic and clinical characteristics. Intent-to-treat analysis revealed a cure rate at day 28 (primary endpoint) of 100% in group A and 99% in group B (difference not significant). The secondary endpoints of mean time to fever clearance (group A ‫ס‬ 34 hours, group B ‫ס‬ 31 hours) and mean time to parasite clearance (group A ‫ס‬ 44 hours group B ‫ס‬ 48 hours) were similar between groups (both differences not significant). Tolerability was good in both treatment groups, with no difference in the overall incidence of adverse events. There was a low incidence of nausea/vomiting (4.9% in both groups) and central nervous system side effects (4.9% in group A versus 8.8% in group B). These were comparable between groups and generally of a mild nature. The three-day combination of artesunate and mefloquine (Artequin, Mepha, Ltd., Aesch, Switzerland) with the introduction of mefloquine on day 1 offers a practical dosing regimen that is highly effective and well tolerated in patients of different ages with uncomplicated P. falciparum malaria. It is likely that the prepacked blister approach translates clinically into a better patient compliance, thereby contributing to limit the development of drug resistance.

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“…The antimalarial efficacy of oral artesunate in uncomplicated malaria appears to be a function of the duration of therapy. 4,5 Recrudescence rates are unacceptably high in patients given less than five days of treatment. Combined treatment with mefloquine improves efficacy and allows shorter courses of artesunate to be given.…”

mentioning

confidence: 99%

Artesunate versus artemether for the treatment of recrudescent multidrug-resistant falciparum malaria.

Price¹,

Vugt²,

Nosten³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. The therapeutic efficacy and toxicity of artesunate (2mg/kg/day for five days, then 1 mg/kg/day for two days: total ϭ 12 mg/kg) was compared with that of artemether (4 mg/kg followed by 2 mg/kg/day for two days, then 1 mg/kg/day for four days: total ϭ 12 mg/kg) for the treatment of recrudescent multidrug-resistant falciparum malaria in an open randomized trial in 443 patients living on the western border of Thailand. Parasite and fever clearance times were similar in both groups; within 48 hr 94% (95% confidence interval [CI] ϭ 91-96%]) of the treated patients were aparasitemic and 93% (95% CI ϭ 89-96%) were afebrile. Symptom resolution and resolution of hepatomegaly were slightly slower in the artesunate group; adjusted hazards ratio ϭ 1.5 (95% CI ϭ 1-2.0, P Ͻ 0.01) and 2.2 (95% CI ϭ 1.4-8, P ϭ 0.04), respectively. There was no significant difference in times to resolution or development of anemia or splenomegaly between treatment groups. By day 28, 3% (95% CI ϭ 0.3-5%) of the patients treated with artesunate and 6% of those treated with artemether (95% CI ϭ 2-9%) had recurrent infections (P ‫؍‬ 0.3). Both regimens were very well tolerated, with no significant adverse effects attributable to either derivative. Overall, these data suggest that the two oral artemisinin derivatives are safe, highly effective, and result in equivalent therapeutic responses in the treatment of drug-resistant falciparum malaria.On the western border of Thailand, Plasmodium falciparum has developed resistance to nearly all the available antimalarial drugs. Mefloquine has been the treatment of choice for uncomplicated falciparum malaria in this region since 1985, but nearly 50% of the patients now fail with high dose (25mg/kg) mefloquine when given alone. 1 These recrudescent infections have a higher failure rate when retreated with mefloquine again, and constitute the reservoir and driving force for drug resistance. 2The artemisinin derivatives are the most potent antimalarial compounds available for human use. 3 They have excellent efficacy against multidrug-resistant strains of P. falciparum and they are very well tolerated. Although more than a million people have now been treated with artemisinin, or one of its derivatives, there is still no consensus concerning the most appropriate dose, treatment regimen, or choice of derivative. The antimalarial efficacy of oral artesunate in uncomplicated malaria appears to be a function of the duration of therapy. 4,5 Recrudescence rates are unacceptably high in patients given less than five days of treatment. Combined treatment with mefloquine improves efficacy and allows shorter courses of artesunate to be given. 6,7 Since 1994, a combination regimen (MAS3) of mefloquine (25 mg/kg) plus a three-day course of artesunate (12 mg/kg) has become the treatment of choice for uncomplicated falciparum malaria in this area.1 The recrudescence rate by day 63 with this treatment is less than 10%, 8 but patients whose infections do recur are symptomatic and their management poses a difficult p...

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Clinical trials of artemisinin and its derivatives in the treatment of malaria in China

Cited by 116 publications

References 0 publications

In vitro study of the anti-cancer effects of artemisone alone or in combination with other chemotherapeutic agents

In vitro study of the anti-cancer effects of artemisone alone or in combination with other chemotherapeutic agents

Artesunate and mefloquine given simultaneously for three days via a prepacked blister is equally effective and tolerated as a standard sequential treatment of uncomplicated acute Plasmodium falciparum malaria: randomized, double-blind study in Thailand.

Artesunate versus artemether for the treatment of recrudescent multidrug-resistant falciparum malaria.

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