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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventy-nine comatose cerebral malaria patients given standard supportive treatment were randomized to receive specific antimalarial chemotherapy of intravenous quinine, intravenous artesunate, or artemisinin suppositories. Artesunate and artemisinin reduced peripheral asexual parasitaemia significantly more rapidly than quinine (90% clearance time 16 h, 18.9 h and 34.5 h respectively), but did not significantly reduce the duration of coma or mortality. The rapid lowering of peripheral parasitaemia may not ameliorate complications already present. These results demonstrate that artemisinin suppositories are as effective as artesunate and quinine given intravenously, and have economic and practical advantages for the treatment of severe malaria in areas remote from major medical centres. However, large numbers of patients will need to be studied if differences in mortality between the 3 treatment groups are to be demonstrated.
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PMID:Comparison of artemisinin suppositories with intravenous artesunate and intravenous quinine in the treatment of cerebral malaria. 128 4

An open paired randomized comparison of intramuscular and intravenous artesunate was conducted in 28 adult patients with severe falciparum malaria. The dose regimen in both groups was 2 mg/kg given immediately followed by 1 mg/kg at 12 and 24 h, and then daily until the patient could swallow. Both routes of administration were well tolerated and there was no evidence of toxicity. One patient in each treatment group died. Clinical and parasitological measures of recovery in survivors were similar in the 2 groups with mean fever clearance times of 37.3 h (standard deviation [SD] = 26.1 h) and 31.5 h (SD = 24.2 h) and mean parasite clearance times of 33.4 h (SD = 13.9 h) and 29.4 h (SD = 12.7 h) in the intravenous and intramuscular groups respectively. Artesunate is equally effective and well tolerated when given by the intravenous or intramuscular routes.
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PMID:An open randomized comparison of intravenous and intramuscular artesunate in severe falciparum malaria. 128 5

Physicians enrolled 127 patients who were admitted to the Bangkok Hospital for Tropical Diseases in Thailand with acute, uncomplicated falciparum malaria between January-May 1991 into a randomized clinical trial of 3 oral treatments: artesunate, mefloquine, and artesunate followed by mefloquine. At the end of 28 days, 88% of patients who received only artesunate (total dose 600 mg), 81% of those who received only mefloquine (total dose 1250 mg), and all patients who received both artesunate and mefloquine were cured. Artesunate reduced the parasite count by 90% within 24 hours of 1st treatment. The 2 groups that received artesunate experienced considerably more rapid reduction in parasitemia and in fever than the group that received only mefloquine (p.002). Mefloquine was more adept than artesunate at clearing residual parasites. Mefloquine-treated patients experienced slightly more headaches and dizziness while they still had malaria than the other 2 groups. The physicians believed that these symptoms could actually have been due to the acute malaria infection. Patients who were on the sequential artesunate-mefloquine regime experienced more nausea and vomiting than the other groups, but the differences were insignificant. The combination therapy with artesunate and mefloquine was very effective and patients with acute, uncomplicated malaria tolerated it well.
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PMID:Randomised trial of artesunate and mefloquine alone and in sequence for acute uncomplicated falciparum malaria. 134 54

A double blind randomized comparative trial of the efficacy of 7-day and 5-day courses of oral artesunate at 600 mg was studied in 89 Thai patients with uncomplicated falciparum malaria. Eighty patients completed the 28-day follow-up period. Artesunate was found to be well tolerated in either regimen. There was an increase of 7% in the cure rate obtained from a 7-day regimen. In 43 patients with a 7-day regimen, the cure rate was 92.5% and 15 patients showed P. vivax in their peripheral blood between days 12 and 34. The mean fever and parasite clearance times were 20 and 40 hours, respectively. In 46 patients with a 5-day regimen, the cure rate was 85% and 8 patients showed P. vivax during days 13 and 24. The mean fever and parasite clearance times were 29 and 40 hours, respectively. Although the cure rates of oral artesunate were high in both regimens, the efficacy was considered unsatisfactory since the aim of the treatment is to achieve 100% cure rate. We suggest however that the extension of the duration of treatment to 7 days together with the increase in total dose may improve therapeutic efficacy of artesunate in falciparum malaria.
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PMID:Double blind randomised clinical trial of two different regimens of oral artesunate in falciparum malaria. 182 Jun 40

Qinghaosu, also known as artemisinin and arteannuin, is a new type of antimalarial drug isolated from Artemisa annua L. Its low solubility in water and oil limited its widespread clinical use. Artesunate (sodium dihydroqinghaosu hydrogen hemisuccinate monoester) is easily soluble in water and is used iv in the treatment of acute cerebral and malignant malaria. However, artesunate was shown to have a very short half-life when given iv in animals as well as in human beings. A transdermal dosage form of artesunic acid had been prepared and was reported to have reliable suppressing and killing effects on plasmobium berghei in mice. This paper reports results of pharmacokinetic studies of this preparation when applied onto a fixed area of the shaved skin of mice and rabbits. Serum concentration of the drug was determined by a method of radioimmunoassay. The drug was found to be easily absorbed from the skin. The serum concentration-time curve is depicted in figures 1. Peak concentration of 1.8 micrograms/ml was reached at about 2 h when a dose of 25 mg/kg was given to rabbits. For mice, peak serum concentrations of 2.05 and 7.11 micrograms/ml were attained in about 0.5 h after doses of 31.3 and 71.4 mg/kg, respectively, while at a dose of 6.7 mg/kg a peak level of 0.82 micrograms/ml (a concentration more than 5000 times the IC50 of artesunate in in vitro tests on plasmodium berghei for antimalarial activity) was attained at about 4 h after application of the drug. The half-lives of the drug were found to be more than 2 h for both mice and rabbits.
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PMID:[The pharmacokinetics of a transdermal preparation of artesunate in mice and rabbits]. 261 77

Studies of 652 adults and children with acute uncomplicated falciparum malaria were done to determine the optimum treatment of multidrug-resistant Plasmodium falciparum malaria on the Thai-Burmese border. Single-dose artesunate (4 mg/kg) plus mefloquine (25 mg of base/kg) gave more rapid symptomatic and parasitologic responses than high-dose mefloquine alone but did not improve cure rates. Three days of artesunate (total dose, 10 mg/kg) plus mefloquine was 98% effective compared with a 28-day failure rate of 31% with high-dose mefloquine alone (relative risk [RR], 0.06; 95% confidence interval [CI], 0.02-0.2; P < .0001). By day 63, the reinfection adjusted failure rates were 2% and 44%, respectively (P < .0001). Artesunate also prevented high-grade failures. Both drugs were well tolerated. No adverse effects were attributable to artesunate. Vomiting was reduced significantly by giving mefloquine on day 2 of treatment (RR, 0.40; 95% CI, 0.20-0.79; P = .009. Artesunate (10 mg/kg over 3 days) plus mefloquine (25 mg/kg) is currently the most effective treatment for falciparum malaria in this area of increasing mefloquine resistance.
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PMID:Treatment of multidrug-resistant Plasmodium falciparum malaria with 3-day artesunate-mefloquine combination. 793 Jul 43

A randomized comparative trial of the pharmacokinetics and pharmacodynamics of oral doses of mefloquine and of mefloquine in combination with artesunate was carried out on 20 Thai male patients with acute, uncomplicated falciparum malaria. The patients were randomized to receive either mefloquine alone (8 patients; 1250 mg of mefloquine--initial dose, 750 mg; followed 6 hours later by 500 mg), or in combination with oral artesunate (12 patients--initial dose, 200 mg of artesunate; followed by 750 mg and 500 mg of mefloquine 6 hours and 12 hours later, respectively). The patients who received mefloquine alone all showed initially good responses to the treatment, with mean + or - SD values for the fever clearance time (FCT) and parasite clearance time (PCT) of 44.7 + or - 43.1 hours and 82.3 + or - 52.3 hours, respectively. 2 patients had recrudescence on day 20 and day 31 (RI response). The cure rate was 75%, and 1 patient had Plasmodium vivax in his peripheral blood on day 52. The patients who received the combination treatment were clinically markedly improved, with a relatively shorter FCT (31.2 + or - 12.4 hours) and significantly shorter PCT (47.5 + or - 19.6 hours). 4 had recurdescences on days 12, 18, 26, and 33; the cure rate was 66%. Artesunate caused 3 significant changes in mefloquine pharmacokinetics: a decrease in the maximum concentration (Cmax: 1623 ng/ml vs. 2212 ng/ml); an increase in the clearance rate (Cl/f:2.9 ml/min/kg vs. 1.1 ml/min/kg); and an expansion of the volume of distribution (Vd/f:31.8 1/kg vs. 25.0 l/kg.
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PMID:Pharmacokinetics of mefloquine alone or in combination with artesunate. 813 Dec 55

Artesunate is an antimalarial agent, available in oral, rectal and parenteral formulations, that provides a rapid clinical effect in patients with Plasmodium falciparum malaria. The rapidity of effect, availability of an intravenous and intramuscular formulation and convenient dosage regimen make artesunate an ideal candidate for the treatment of severe malaria, including cerebral disease. While some results have been promising, there is no clear evidence to date that artesunate reduces mortality in patients with cerebral malaria to any greater extent than standard quinine therapy. When given as monotherapy, treatment should be continued for at least 5 to 7 days to prevent recrudescence. Combination therapy with mefloquine allows artesunate to be administered over 3 days or less, with a satisfactory clinical outcome maintained. Although optimal dosages remain to be determined, this combination continues to provide the rapid onset of clinical effect observed with artesunate monotherapy, but decreases the rate of recrudescence to 2% (i.e. radical cure rate of 98%) when used as treatment in patients with uncomplicated malaria from areas with a high risk of multidrug-resistance falciparum malaria. Although assessment of tolerability is complicated by the difficulty of distinguishing between disease- and treatment-related events, artesunate and artesunate-mefloquine combinations appear to be well tolerated in adults and children. Indeed, it is possible that prior administration of artesunate may reduce the incidence of mefloquine-induced vomiting. Clinical findings to date have not revealed any pattern of resistance to artesunate after use of the drug. However, given the history of the development of resistance to other antimalarial drugs, the use of artesunate should be restricted to areas of multidrug resistance, the drug should be used in combination with a longer acting agent such as mefloquine, and it should be used in regimens that provide radical cure rates of 90 to 100%. If used according to these treatment principles, artesunate will provide a well tolerated and valuable addition to the current extremely limited treatment options for multidrug-resistant falciparum malaria, a widespread parasitic disease associated with considerable mortality.
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PMID:Artesunate. A review of its pharmacology and therapeutic efficacy in the treatment of malaria. 853 55

The in vivo and in vitro effects of antimalarials on cytoadherence and rosette formation were studied in 17 patients with severe and 46 with uncomplicated falciparum malaria. Cytoadherence was increased in severe malaria (P<.001). Artesunate and artemether were more potent than quinine in inhibiting both adherence properties. Artesunate was the most rapidly acting drug tested, producing >50% inhibition of both cytoadherence and rosetting in vivo and in vitro within 2 hr of drug exposure. Exposure to quinine for > or = to 4 h in vivo reduced rosetting by >50%, but not cytoadherence. Quinine did not reduce cytoadherence or rosetting significantly in vitro with exposure times of < or = to 8 h. These results suggest that artemisinin derivatives are more effective than quinine in preventing pathologic processes in parasitized erythrocytes that contribute to microvascular obstruction in severe malaria.
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PMID:Antimalarial drugs reduce cytoadherence and rosetting Plasmodium falciparum. 862 34

Artesunate, the only artemisinin analogue that can be given intravenously, produces rapid parasite and fever clearance in falciparum malaria. A significant therapeutic problem is a high, late recrudescence rate, probably due to short half-lives of both artesunate and its active metabolite dihydroartemisinin relative to conventional dosing intervals. One method of extending the duration of action of artesunate could be to administer the drug by infusion rather than bolus injection, provided that it is chemically stable at ambient temperature. Artesunate was found to be stable in 0.9% w/v sodium chloride at 9 degrees C, 23 degrees C and 36.5 degrees C for 130, 10.6 and 1.6 h, respectively. Interpolating from an Arrhenius plot, artesunate should be stable for approximately 4 h at 30 degrees C, a temperature representative of ambient conditions in tropical countries. Exposure to light did not affect the degradation rate. Single compartment pharmacokinetic modelling was used to evaluate potential differences in artesunate and dihydroartemisinin plasma concentrations following administration of artesunate by intravenous bolus or infusion. A bolus injection of artesunate at a dose of 4 mg kg-1 gives a peak concentration of 5.3 mg L-1, falling to 0.005 mg L-1 at 5 h. The same dose infused over 4 h results in a peak concentration of 0.92 mg L-1, falling to 0.005 mg L-1 at 8 h. Simultaneous modelling of dihydroartemisinin showed that while its peak plasma concentration was reduced by 27% and the peak delayed by 2.5 h following artesunate administration by infusion, substantially higher concentrations were maintained compared with those predicted after bolus artesunate. These data indicate that artesunate can be administered as a high-dose intravenous infusion, thus avoiding high plasma concentrations. This strategy also has the potential to prolong the duration of antimalarial effect and reduce toxicity, and consequently improve clinical outcome in seriously ill patients.
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PMID:Chemical stability of artesunate injection and proposal for its administration by intravenous infusion. 872 89


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