Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Artemether”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1998

Positioning, labelling, and medical information control of co-artemether tablets (CPG 56697): a fixed novel combination of artemether and benflumetol. Novartis Co-Artemether International Development Team.

Coartemether is a fixed 1:6 ratio of artemether and lumefantrine (benflumetol), a joint development between Novartis Pharma and the Academy of Military Medical Sciences (Beijing, China). It is well tolerated and has a high efficacy against uncomplicated and drug resistant falciparum malaria by oral administration. The preclinical profile of coartemether revealed no prohibitive toxicological, teratogenic or mutagenic findings. No evidence of neurotoxicity was seen in oral preclinical studies. It shows a negative response to the induction of resistance and prevents recrudescence. Clinically, coartemether shows a rapid onset of antiparasitic action, resolution of symptoms, no clinical neurotoxicity and excellent parasite clearance.

Administration, Oral↗
PubMed1996

Activity of artemether-azithromycin versus artemether-doxycycline in the treatment of multiple drug resistant falciparum malaria.

The efficacy of the combination of artemether with doxycycline or azithromycin was evaluated in 60 patients with acute uncomplicated falciparum malaria who attended malaria clinic in Mae Sot, Tak Province (Thai-Myanmar border). Patients (30 each) were randomized to receive (a) 300 mg artemether together with 100 mg doxycycline as initial doses, followed by 100 mg artemether plus 100 mg doxycycline at 12 hours later, then 100 mg doxycycline every 12 hours for another 4 days, or (b) 300 mg artemether together with 500 mg azithromycin, followed by 250 mg azithromycin at 24 and 48 hours. The follow-up period was 28 days. Patients in either group had a rapid initial response to treatment with comparable PCT and FCT. The cure rate of artemether-azithromycin regimen was significantly lower than that of artemether-doxycycline regimen (14.8 vs 53.3%). Low cure rate from artemether-azithromycin combination in this study was likely to be due to inadequate azithromycin dosage. However, with the low incidence of gastrointestinal adverse effects, the once daily dose of azithromycin could still be increased in order to enhance its clinical efficacy. The simplicity of drug administration and lesser incidence of adverse effects make azithromycin a more proper partner of artemether than doxycycline. Further dose-finding and pharmacokinetic study with the artemether-azithromycin combination is encouraging.

Adolescent↗
PubMed1995

A comparative clinical trial of artemether and the sequential regimen of artemether-mefloquine in multidrug resistant falciparum malaria.

A randomized, comparative clinical trial for assessment of the efficacy of two antimalarial regimens, artemether alone and the sequential regimen artemethermefloquine, was carried out in 109 Thai male patients with acute uncomplicated, multidrug resistant falciparum malaria who were admitted to the Bangkok Hospital for Tropical Diseases. Fifty-three patients received oral artemether at a total dose of 700 mg (300 mg initially, followed by 100 mg daily for 4 days), and 56 patients received the sequential regimen of artemether-mefloquine (300 mg oral artemether initially, followed by 750 mg oral mefloquine after 24 h). Patients in both groups had a rapid initial response to treatment, with a median parasite clearance time of 40 h compared with 43.5 h for the sequential regimen. Median fever clearance times were 42.5 h and 32.5 h for artemether and the sequential regimen respectively. Parasitaemia reoccurred in patients of both groups during the follow up period, six in the artemether and three in the sequential regimen (cure rates were 88 and 94%). No serious adverse effects were observed in either group of patients.

Administration, Oral↗
PubMed1998

Plasma concentrations of artemether and its major plasma metabolite, dihydroartemisinin, following a 5-day regimen of oral artemether, in patients with uncomplicated falciparum malaria.

Plasma concentrations of artemether and its active plasma metabolite (dihydroartemisinin) were measured in 49 male, Thai patients with acute, uncomplicated, multidrug-resistant, Plasmodium falciparum malaria, following their treatment with oral artemether (300 mg on the first day, then 100 mg daily for another 4 days). Four patients recrudesced (on days 19-22). After the first dose, artemether became undetectable in < or = 18 h and this drug was also undetectable in samples collected immediately before each dose. Although dihydroartemisinin followed similar trends, three patients had detectable plasma concentrations of this metabolite 24 h after the first dose (i.e. immediately before the second dose). Median (range) values for plasma concentrations of dihydroartemisinin 6 h [354 (150-751) v. 196 (178-220) ng/ml] and 12 h [158 (25-420) v. 54 (25-115) ng/ml] after the initial dose, estimated antimalarial activities (calculated as dihydroartemisinin equivalents) 6 h [331 (78.2-644.1) v. 23 (183.3-270) nmol/litre] and 12 h [98.3 (10-192.2) v. 56.7 (9.8-59.4) nmol/litre] after the initial dose, and the corresponding 'areas under the curves' (AUC) [3684 (1562-8216) v. 834 (1401-2030) ng.h/ml] were all significantly higher in the patients with sensitive responses than in those who recrudesced.

Acute Disease↗
PubMed2002

Artemether-lumefantrine for treating uncomplicated falciparum malaria.

BACKGROUND: Artemether-lumefantrine is being promoted by the World Health Organization for treating uncomplicated malaria. It is expensive. We sought evidence of its superiority over existing treatment regimens. OBJECTIVES: To compare artemether-lumefantrine with other antimalarial drugs for treating uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized trials register (April 2002), the Cochrane Controlled Trials Register (Issue 2, 2002), MEDLINE (1966 to April 2002), EMBASE (1988 to April 2002), conference proceedings, and reference lists of articles. We contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine. SELECTION CRITERIA: Randomized and quasi-randomized trials comparing artemether-lumefantrine administered orally with standard treatment regimens (single drug or combination). DATA COLLECTION AND ANALYSIS: Two reviewers independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data. Parasitaemia on day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome. Adverse event information was collected from the studies. MAIN RESULTS: Eight trials (2117 participants) met the inclusion criteria. In the four studies against single agents, failure rates for artemether-lumefantrine tended to be higher in comparisons against sulfadoxine-pyrimethamine, halofantrine, and mefloquine. This difference was statistically significant for mefloquine. When compared with chloroquine, artemether-lumefantrine was better in two studies, but the failure rate for chloroquine at these sites was over 50%. All single agent studies used four doses of artemether-lumefantrine. In comparisons against combination treatment, three trials tested artemether-lumefantrine against mefloquine-artesunate and showed that artemether-lumefantrine was inferior for day 28 cure (Relative Risk 6.33, 95% confidence interval 3.08 to 13.01). If this comparison is confined to the two trials where participants received six doses, artemether-lumefantrine was associated with higher cure rates, but this was not statistically significant (Relative Risk 4.20, 95% confidence interval 0.55 to 31.93). REVIEWER'S CONCLUSIONS: Artemether-lumefantrine is more effective than chloroquine in chloroquine resistant areas. Artemether-lumefantrine is less effective than mefloquine or mefloquine combined with artesunate. We found no evidence to confirm or refute whether artemether-lumefantrine was better than sulfadoxine-pyrimethamine.

Antimalarials↗
PubMed1997

Pharmacokinetics and bioavailability of oral and intramuscular artemether.

OBJECTIVE: The pharmacokinetics and bioavailability of artemether and dihydroartemisinin were investigated in eight Thai males following the administration of single oral and intramuscular doses of artemether (300 mg) in a randomized two-way cross-over study. RESULTS: Both oral and intramuscular artemether were well-tolerated. In most cases, artemether and dihydroartemisinin were detected in plasma after 30 min and declined to levels below the limit of detection within 18-24 h. Compared with intramuscular administration, oral administration of artemether resulted in a relatively rapid but incomplete absorption [Cmax: 474 vs 540 ng.ml-1; tmax: 2.0 vs 3.9 h; AUC: 2.17 vs 5.20 micrograms.h.ml-1]. Geographic means of lag-time and absorption half-life (t1/2a) of oral vs intramuscular artemether were 0.28 and 1.1 h vs 0.30 and 2 h, respectively, t1/2z was significantly shortened after the oral dose [2.8 vs 6.9 h]. Mean oral bioavailability relative to intramuscular administration was 43.2%. The ratio of the AUCs of artemether to dihydroartemisinin was significantly lower after the oral than after the intramuscular dose (geometric mean: 0.29 vs 0.60). artemisinin, which is commercially available in China, Vietnam, Thailand and some African countries. The drug is administered as solution in oil for intramuscular injection or as oral tablets. The clinical efficacy of artemether is dependent on the formulation, dosing scheme, duration of treatment, and the severity of the disease [1, 2]. Oral artemether is effective but with short-term treatment, the relapse rate is high. While the efficacy of intramuscular artemether against multidrug-resistant P. falciparum in either uncomplicated or severe cases has been confirmed, its pharmacokinetic documentation is limited. Formulations with high bioavailability and low costs are essential. With high-performance liquid chromatography and electrochemical detection, more sensitive and reliable assay of artemisinin and derivatives in biological fluids has been achieved [3-4]. In the present study, we have assessed the pharmacokinetics and bioavailability of oral and intramuscular artemether, in healthy Thai males.

Administration, Oral↗
PubMedDate not supplied

The contribution of the enzymes CYP2D6 and CYP2C19 in the demethylation of artemether in healthy subjects.

The contribution of the enzymes CYP2D6 and CYP2C19 to the metabolism of artemether was evaluated in a cross-over study in seven healthy adult Caucasian subjects. The pharmacokinetic properties of artemether and its active metabolite dihydroartemisinin were compared when given 100 mg artemether orally alone or in combination with either CYP2D6-inhibitor quinidine or CYP2C19-inhibitor omeprazole. Plasma concentrations of artemether and dihydroartemisinin were measured with reversed phase high performance liquid chromatography with electro-chemical detection (HPLC-ED). Artemether was rapidly absorbed with a mean tmax of 0.8 h (95% confidence interval, CI=0.5-1.1) reaching a mean Cmax of 29 ng/ml (14-45 ng/ml). The mean elimination half-life was 1.3 h (0.8-1.8 h). The pharmacokinetic parameters for dihydroartemisinin were not significantly different from those for artemether. Artemether combined with quinidine revealed no significant changes in the plasma concentrations of either artemether or dihydroartemisinin. No changes were seen in the combination with omeprazole as a CYP2C19 inhibitor. A second peak in the plasma concentration profile was observed 2-4 h after drug intake. This phenomenon was possibly related to variable gastric emptying. No major contribution of the enzymes CYP2D6 or CYP2C19 was found in artemether metabolism. No interethnic differences in artemether metabolism on the basis of a genetic polymorphism of these enzymes is to be expected.

Administration, Oral↗
PubMed2000

Pharmacokinetic interaction trial between co-artemether and mefloquine.

Forty-two healthy subjects were randomized in a parallel three-group design trial to investigate potential electrocardiographic and pharmacokinetic interactions between the new antimalarial co-artemether, a combination of artemether and lumefantrine (both of which are predominantly metabolized through CYP3A4), and mefloquine, another antimalarial described as a substrate (and possible inhibitor) of CYP3A4. Subjects were assigned to one of the three possible treatment groups (i.e., co-artemether alone or mefloquine alone or the combination of both). The dosage was 1000 mg mefloquine (divided into three doses over 12 h) followed 12 h later by six applications of co-artemether (40 mg artemether+480 mg lumefantrine each) over 60 h. The study medications were generally well tolerated after all treatments. Concomitant administration with mefloquine caused statistically significant lower (around 30-40%) plasma concentrations of lumefantrine than when co-artemether was administered alone. Even if important, this decrease in lumefantrine exposure was considered unlikely to impact clinical efficacy given the wide therapeutic index of co-artemether and the usual high variability in lumefantrine plasma levels, mostly and more importantly influenced by food intake. However, patients should be encouraged to eat at dosing times to compensate for this decreased bioavailability. The pharmacokinetics of artemether, DHA or mefloquine were not affected. Artemether concentrations significantly decreased over doses, independently of mefloquine co-administration, while DHA concentrations slightly (not significantly) increased. Therefore, no clinically relevant risks due to pharmacokinetic drug-drug interaction are expected at the enzymatic level following co-administration of co-artemether with CYP3A4 substrates with similar affinity to that of mefloquine.

Adult↗
PubMed1998

Population pharmacokinetics and therapeutic response of CGP 56697 (artemether + benflumetol) in malaria patients.

AIMS: To investigate the pharmacokinetic and pharmacodynamic properties of artemether and benflumetol in a fixed combination tablet (CGP 56697) and to offer an explanation for the lower than expected cure rate in a Thai clinical trial. METHODS: Two hundred and sixty patients were enrolled into a randomized, double-blind, parallel group, dose-finding trial. CGP 56697 was given orally, either as: A, 4 x 4 tablets over 48 h; B, 4 x 2 tablets over 48 h or C, 3 x 4 tablets over 24 h. Each tablet contained artemether 20 mg amd benflumetol 120 mg. The pharmacokinetics were determined using a population-based approach combining full profiles (42 patients) and sparse data (218 patients). Parasite clearance time and 28 day cure rate were correlated with the derived pharmacokinetic parameters. RESULTS: The median absorption half-life of benflumetol was 5.3 h, with a tmax of 10 h and terminal elimination half-life of 4.5 days. For artemether (and its metabolite, dihydroartemisinin), the corresponding values were 1.9 (1.9) h, 1.8 (1.2) h, and 0.84 (0.43) h. The variability in bioavailability of artemether and dihydroartemisinin was large both between doses and between patients, but was less pronounced for benflumetol. Compared with the first dose, benflumetol bioavailability was estimated to increase three-fold by the third and fourth doses. Higher artemether or dihydroartemisinin AUC was found to decrease parasite clearance time. Higher benflumetol AUC was found to significantly increase the chance of cure. CONCLUSIONS: Using a population-based approach it was confirmed that the pharmacokinetic and pharmacodynamic properties of benflumetol and artemether differ markedly. Benflumetol AUC is associated with cure and the effect of benflumetol when coadministered with artemether is to prevent recrudescence. The mode of action of benflumetol is consistent with its longer elimination half-life. A short course of low-dose artemether, which is rapidly absorbed and has a short elimination half-life, produced effective parasite clearance. The complementary pharmacokinetic and pharmacodynamic properties of benflumetol and artemether was the main rationale for developing a fixed-dose combination. While the 4 x 4 dose regimen is very effective in most endemic areas, the poorer absorption (2.5 fold lower than in China) and the more resistant parasites in Thailand require higher doses of this drug.

Adolescent↗
PubMed2000

Oral artemether for prevention of Schistosoma mansoni infection: randomised controlled trial.

BACKGROUND: Chemotherapy with praziquantel is the current strategy of choice to control schistosomiasis. However, in view of concern about praziquantel tolerance or resistance, new drugs are needed. Artemether, a derivative of the antimalarial drug artemisinin, kills immature schistosomes of Schistosoma japonicum, and reduces the incidence of infection in field trials. Laboratory studies have also showed activity by this drug against S. mansoni. We report a randomised double-blind placebo-controlled clinical trial of artemether to prevent S. mansoni infection. METHODS: The trial was done in an area of western Côte d'Ivoire endemic for S. mansoni. 354 schoolchildren were enrolled. Stool specimens were screened over four consecutive days, followed by two mass treatments with praziquantel 4 weeks apart. All S. mansoni negative children were randomly assigned to placebo (n=151) or artemether 6 mg/kg (n=138) orally six times once every 3 weeks. Adverse events were assessed 24 h after treatment. Perceived illness episodes were recorded once a week by interviewing the children with a standardised questionnaire. 3 weeks after the final medication S. mansoni infections were assessed by screening stool samples. Blood samples were examined for Plasmodium falciparum before the first and after the last artemether treatment. FINDINGS: Oral artemether showed no adverse reactions. The group that received artemether had a significantly lower incidence of S. mansoni infection (31/128 versus 68/140, relative risk: 0.50 [95% CI 0.35-0.71], p=0.00006). The geometric mean egg output among positive children in the artemether group was significantly lower than in placebo recipients (19 vs 32 eggs/g stool, p=0.017). There was also a significant reduction in the prevalence of P. falciparum. INTERPRETATION: Oral artemether is safe and shows a prophylatic effect against S. mansoni. The use of artemether may be recommended in appropriated situations as an additional tool for more effective schistosomiasis control measures. However the application needs to be carefully assessed especially in view of the concern that it could select for resistant plasmodia.

Administration, Oral↗
PubMed1999

Multiple dose pharmacokinetics of artemether in Chinese patients with uncomplicated falciparum malaria.

Multiple dose pharmacokinetics of artemether and dihydroartemisinin were investigated in chinese patients treated for malaria. They received over 2 days either 4 x 80 mg artemether orally (n = 48) or 4 x 80-480 mg co-artemether (n = 40), a combination of artemether and lumefantrine (benflumetol). Lag time = 0.48 h (mean), Cmax after first dose = 157 ng/ml, t(max) = 1.73 h and elimination half-life = 1.16 h. The lag and absorption times were 0.5 h longer for co-artemether compared with artemether. Dihydroartemisinin paralleled artemether pharmacokinetics. Artemether Cmax after the last dose was one-third of the Cmax after the first dose while, inversely, dihydroartemisinin Cmax increased over time. We suggest that auto-induction of gut mucosa enzymes and/or liver enzymes causes a time-dependent increase in first-pass metabolisation of artemether.

Adolescent↗
PubMed1996

Artemether-pyrimethamine in the treatment of pyrimethamine-resistant falciparum malaria.

In vitro susceptibility and clinical response of multidrug resistant Plasmodium falciparum to the combination artemether-pyrimethamine were evaluated in patients with acute uncomplicated falciparum malaria. Sixty patients were randomized to receive 3 oral regimens of the combination artemether-pyrimethamine as follows: Regimen-I: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then placebo on the two consecutive days; Regimen-II: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then artemether (150 mg) plus pyrimethamine (50 mg) on the second day, and placebo on the third day; Regimen-III: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then artemether (150 mg) plus pyrimethamine (50 mg) on the second and third days. All patients had a rapid initial response to treatments with 95% of parasitemia being cleared within the first 24 hours. PCT24hours and PCT48hours were similar among the three drug regimens (11 vs 4, 6 vs 12, and 9 vs 11 patients for a 1-day, 2-day, and 3-day combination regimen, respectively). Fever was cleared within 48 hours in all patients in either group. Transient mild nausea, vomiting and loss of appetite were found in a few patients during the first 2 days of treatment. Seven patients did not complete the 28 day follow-up period (5 vs 2 in a 1-day vs 2-day regimen), the reason for withdrawal was not associated with drug-related adverse effects. Only 53 patients were therefore qualified for the efficacy assessment. There was 15, 13 and 5 patients in a 1-day, 2-day and 3-day combination regimens, respectively, who had reappearance of the parasitemia between days 11 and 21. The cure rates of the 3 treatment groups were statistically significantly different (0, 27.8, and 75% for a 1-day, 2-day and 3-day combination regimen, respectively). Two patients developed P. vivax malaria on days 20 and 24. All of the isolates were highly resistant to pyrimethamine, with MIC of 10(-5) M. There is potential advantage of this combination therapy in reducing the dosage and treatment period of artemisinin derivative, which is therefore likely to improve complaince in clinical practice. The use of a 3-day combination regimen (300 mg artemether plus 100 mg pyrimethamine on the first day, then 150 mg artemether plus 50 mg pyrimethamine on the second and third days) seems to be a good alternative regimen to sulfadoxine/ pyrimethamine in areas where P. falciparum is sensitive to pyrimethamine eg in Africa.

Adolescent↗
PubMed2000

Cardiac effects of co-artemether (artemether/lumefantrine) and mefloquine given alone or in combination to healthy volunteers.

UNLABELLED: Co-artemether is an oral tablet of artemether (20 mg) and lumefantrine (120 mg) for the treatment of falciparum malaria. Administration in the presence of mefloquine is likely, as co-artemether may be used following failure of antimalarial prophylaxis or treatment with mefloquine. OBJECTIVE: The effects on the QTc interval were compared among treatment with three doses of mefloquine (500, 250, 250 mg over 12 h) followed by six doses of co-artemether (6 x 4 tablets over 60 h) and either treatment alone. The study was performed in a randomised, double-blind, parallel group design in 14 healthy male subjects per dose group. METHODS: Electrocardiograms (ECGs) were recorded before dosing and repeatedly thereafter. The Bazett formula was used to calculate the QTc interval. The maximum and average QTc intervals for the first, third and sixth dosing intervals of co-artemether treatment were compared among treatments. Drug plasma concentrations were determined at identical times with the ECG recordings for exploratory pharmacokinetic/pharmacodynamic evaluation. RESULTS: No clinically relevant differences in the QTc interval were observed after sequential administration of mefloquine and co-artemether relative to either treatment given alone, and there were no clinically relevant study drug-related effects on the QTc interval after either treatment. Plasma drug measurements revealed adequate systemic exposure to artemether, dihydroartemisinin, lumefantrine and mefloquine, well in line with the clinical setting. No correlation between the length of the QTc interval and plasma drug concentrations was found for any of the compounds. CONCLUSIONS: Untoward effects on the QTc interval are unlikely to occur when co-artemether is administered following prophylaxis or treatment with mefloquine.

Adult↗
PubMed1992

Comparison of oral artemether and mefloquine in acute uncomplicated falciparum malaria.

Plasmodium falciparum malaria in Thailand is highly resistant to available antimalarials, and alternative drugs are needed urgently. Artemether is effective against falciparum malaria but associated with a high recrudescence rate. The proper dosage regimen remains to be defined. We have done a clinical trial comparing mefloquine 1250 mg in divided doses with oral artemether at 700 mg total dose given over 5 days in acute uncomplicated falciparum malaria. 46 patients, admitted to the Bangkok Hospital for Tropical Diseases, were randomised to receive either mefloquine (12) or artemether (34). Hospital follow-up was 28 days for the artemether group and 42 days for the mefloquine group. Oral artemether gave a significantly faster parasite clearance time than mefloquine (30 vs 64 h), and a significantly better cure rate (97 vs 64%) with fewer episodes of dizziness and vomiting. Oral artemether at 700 mg given over 5 days is effective and well tolerated. The cure rate with this regimen is higher than that reported by previous studies with 600 mg intramuscular artemether given over 5 days. Oral artemether can be considered as an alternative drug for multiple-drug-resistant falciparum malaria.

Acute Disease↗
PubMed2000

Effect of artemether against Schistosoma haematobium in experimentally infected hamsters.

The drug, artemether, has been shown to be active against the juvenile stages of Schistosoma japonicum and Schistosoma mansoni in experimentally infected animals, while it is less effective on adult worms. These findings have been confirmed in randomised controlled trials in humans. Consequently, it could be expected that artemether is also active against Schistosoma haematobium. We present here the first results from experiments assessing the effect of artemether on S. haematobium. Hamsters with a single infection received intra-gastrically an initial dose of 300 mg/kg artemether on day 14, 21 or 28, followed by further doses at varying treatment regimens. In all the treatment groups, the total and female worm reduction rates were highly significant, and ranged from 78 to 100% in hamsters harbouring juvenile schistosomes. Hamsters infected three times with S. haematobium, on days 0, 4 and 9, and repeatedly treated with artemether at the same dose as above, showed highly significant total and female worm reduction rates of between 94 and 99%. Artemether was also active against 77-day-old adult S. haematobium, since its administration on two consecutive days resulted in highly significant total and female worm reduction rates of 76-89%. Our findings confirm that artemether is also active against S. haematobium, especially the schistosomules. These results provide a basis for clinical trials in humans, for further assessment of the potential of artemether for schistosomiasis control.

Animals↗
PubMed1997

Open randomized trial of oral artemether alone and a sequential combination with mefloquine for acute uncomplicated falciparum malaria.

One hundred fifty-one patients with acute uncomplicated falciparum malaria were enrolled in a randomized, open-label study of oral artemether given alone for five or seven days or a sequential treatment of oral artemether followed by mefloquine. Forty patients received oral artemether, 100 mg initially, then 50 mg every 12 hr for a total dose of 500 mg over a five-day period: Group I. Fifty-eight patients received oral artemether, 100 mg initially, then 50 mg every 12 hr for a total dose of 750 mg over a seven-day period: Group II. Fifty-three patients received oral artemether, 200 mg every 8 hr for a total dose of 600 mg, followed 8 hr later with mefloquine (1,250 mg divided into two doses given 6 hr apart: Group III. All patients were admitted to the hospital for 28 days to exclude reinfection and 131 patients remained through the 28-day follow-up. Only two, nine, and nine patients in Groups I, II, and III, respectively, left the hospital prior to study completion for reasons unrelated to their treatment. Cure rates for the three groups were 74% (28 of 38) for Group I, 98% (48 of 49) for Group II, and 98% (43 of 44) for Group III. Mean fever and parasite clearance times were not significantly different (32.8, 27.5, and 31.4 hr for fever clearance times and 40.2, 40.6, and 36.7 hr for parasite clearance times of Groups I, II, and III, respectively) nor were any adverse effects seen. In vitro drug susceptibility testing of admission and recrudescent parasite isolates was conducted for 10 patients. These data showed no decreased response to artemether or dihydroartemisinin in recrudescent isolates when compared with admission isolates. The results of this study suggest that sequential treatment for two days with oral artemether (600 mg) followed by mefloquine (1,250 mg) is effective and well-tolerated in patients with acute uncomplicated falciparum malaria and may be an alternative treatment for multidrug-resistant falciparum malaria, particularly useful for treating patients in rural areas where the period of admission to the hospital should be as short as possible. A seven-day regimen of artemether alone (750 mg) is also very effective, yet requires prolonged administration of drug after malaria symptoms disappear.

Administration, Oral↗
PubMed2000

Artemether, an effective new agent for chemoprophylaxis against shistosomiasis in China: its in vivo effect on the biochemical metabolism of the Asian schistosome.

Conventional drug chemotherapy against human schistosomiasis currently relies on treatment with praziquantel to eliminate adult schistosome worm pairs. The use of praziquantel for control purposes is limited, however, by high rates of post-treatment re-infection with subsequent parasite egg deposition and host end-organ damage. Artemether, a methyl ether derivative of the anti-malarial drug quinghaosu, was discovered recently to also have anti-schistosomal properties. Because artemether selectively targets the larval migratory stages of the parasite, known as schistosomulae, it blocks the development of ovipositing adult schistosome worm pairs in the vasculature. On this basis, we have since shown in clinical trials conducted in China that artemether has proven benefit as an agent for chemoprophylaxis. In vivo studies using laboratory animals suggest that artemether causes damage to the tegument and musculature of schistosomulae. Artemether may exert its helminthotoxic effect through synergy with hemin or related heme-containing compounds. Schistosomes recovered from artemether treated laboratory animals have increased glycogen phosphorylase activity, but decreased glucose uptake. These findings may account for their decreased glycogen content, relative to schistosomes recovered from untreated laboratory animals. The artemether-damaged schistosomes also have decreased activities of a number of enzymes and enzyme systems, including glycolysis. This might suggest common pathways by which artemether may target human parasites that live in the bloodstream.

Animals↗