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Archives de Pediatrie : Organe Officiel... Apr 2005To evaluate mefloquine versus halofantrine in children suffering from acute uncomplicated falciparum malaria. (Clinical Trial)
Clinical Trial
AIM OF THE STUDY
To evaluate mefloquine versus halofantrine in children suffering from acute uncomplicated falciparum malaria.
MATERIAL AND METHODS
Prospective non randomized study in hospitalized children during one year. Acute falciparum malaria was defined by fever and a positive thin and/or thick smear. Malaria was presumed to have been contracted in Comoros archipelago and/or Madagascar 6 months previously. Patients were excluded, when quinine had to be used, according to World Health Organization's severity criteria.
RESULTS
Forty-nine children were included: 29 were treated with halofantrine and 20 with mefloquine. Patients features in the two groups of treatment were identical, with exception for the mean time between first clinical signs and diagnosis (shorter in mefloquine group). Fever's and hospitalization's duration under treatment were similar. An increase in QTc interval was frequently observed in patients treated with halofantrine (56 versus 0%), although patients with mefloquine experienced vomiting (45 versus 0%). Relapses seemed to be more frequent with halofantrine (14 versus 0%).
DISCUSSION
Halofantrine and mefloquine are efficient for falciparum malaria treatment in our pediatric series, despite a high rate of adverse events. Mefloquine's tolerance may probably be improved with changes in regimen and dose. Relapses are more frequent with a single first treatment of halofantrine, than with mefloquine. Unfortunately, features of a second halofantrine treatment are not defined.
Topics: Adolescent; Antimalarials; Child; Child, Preschool; Female; Humans; Infant; Long QT Syndrome; Malaria, Falciparum; Male; Mefloquine; Phenanthrenes; Treatment Outcome
PubMed: 15893244
DOI: 10.1016/s0929-693x(05)80017-x -
Military Medicine Mar 2023To evaluate the associations between neurocognitive and psychiatric health outcomes with mefloquine or any antimalarial exposure.
INTRODUCTION
To evaluate the associations between neurocognitive and psychiatric health outcomes with mefloquine or any antimalarial exposure.
MATERIALS AND METHODS
Medical records were systematically reviewed to identify veterans that indicated antimalarial medication use. Linear regression was performed to examine associations between mefloquine/antimalarial exposure and health outcomes. The mefloquine-exposed group was further compared with normative populations for the same health outcomes.
RESULTS
In the adjusted models, no significant differences were noted between the two exposure groups and the unexposed group for any of the health measures (P-value > 0.05). When compared to normative population samples, the mefloquine-exposed group had poorer health and greater neurobehavioral symptom severity or cognitive complaints.
CONCLUSION
This study suggests that mefloquine use by veterans referred for intensive evaluation of their military deployment exposures and health was not associated with increased, long-term, neurocognitive/psychiatric symptoms compared to unexposed veterans.
Topics: Humans; Mefloquine; Antimalarials; Veterans; Cross-Sectional Studies; Cohort Studies
PubMed: 35446430
DOI: 10.1093/milmed/usac104 -
Memorias Do Instituto Oswaldo Cruz 1992Based on the results of in vitro sensitivity of Plasmodium falciparum to chloroquine, quinine and mefloquine, and evaluation of drug consumption conducted in 1987-1988...
Based on the results of in vitro sensitivity of Plasmodium falciparum to chloroquine, quinine and mefloquine, and evaluation of drug consumption conducted in 1987-1988 in four areas in the north and south-west of Cameroon, two opposite situations were encountered in this country. In northern Cameroon where mefloquine resistance is prevalent a close correlation was found between the responses of P. falciparum to mefloquine and to quinine, but not between mefloquine and chloroquine. In the south, where chloroquine resistance is highly prevalent, no correlation was found neither between mefloquine and chloroquine nor mefloquine and quinine, but the responses to quinine and chloroquine appear partly correlated. These results lead to formulate the hypothesis of a "southern" type of P. falciparum submitted to a high chloroquine drug pressure inducing a secondary cross resistance, whilst a "northern" type submitted to a relatively high and abortive quinine drug pressure inducing a primary quinine resistance and a secondary cross resistance with mefloquine.
Topics: Animals; Cameroon; Carrier State; Child; Child, Preschool; Drug Resistance; Drug Utilization; Humans; Infant; Malaria, Falciparum; Mefloquine; Plasmodium falciparum; Quinine
PubMed: 1343701
DOI: 10.1590/s0074-02761992000700045 -
PLoS Neglected Tropical Diseases 2009The treatment and control of schistosomiasis, an often neglected tropical disease that exacerbates poverty, depends on a single drug, praziquantel. The large-scale use...
BACKGROUND
The treatment and control of schistosomiasis, an often neglected tropical disease that exacerbates poverty, depends on a single drug, praziquantel. The large-scale use of praziquantel might select for drug-resistant parasites, hence there is a need to develop new antischistosomal compounds. Here, we report that the antimalarial drug mefloquine possesses promising antischistosomal properties in mice.
METHODOLOGY/PRINCIPAL FINDINGS
A single dose of mefloquine (200 or 400 mg/kg) administered orally to mice infected with adult Schistosoma mansoni or adult S. japonicum resulted in high or complete total and female worm burden reductions (72.3%-100%). Importantly, high worm burden reductions were also observed for young developing stages of S. mansoni and S. japonicum harbored in the mouse. Both mefloquine erythro-enantiomers resulted in high and comparable total and female worm burden reductions when given to mice with either a sub-patent or patent S. mansoni infection.
CONCLUSIONS/SIGNIFICANCE
Our findings hold promise for the development of a novel antischistosomal drug based on an aminoalcohol functionality. Further in vitro and in vivo studies have been launched to elucidate the possible mechanism of action and to study the effect of mefloquine on S. haematobium and other trematodes. It will be interesting to investigate whether mefloquine, which is widely and effectively used for the treatment of malaria, has an impact on schistosomiasis in areas where both malaria and schistosomiasis co-exist.
Topics: Administration, Oral; Animals; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Female; Male; Mefloquine; Mice; Mice, Inbred Strains; Schistosoma japonicum; Schistosoma mansoni; Schistosomicides
PubMed: 19125172
DOI: 10.1371/journal.pntd.0000350 -
Clinical Pharmacology and Therapeutics Oct 1990Mefloquine pharmacokinetics were compared in a randomized clinical trial in Thailand among patients with malaria and healthy volunteers. A single oral dose of 1500 mg... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Mefloquine pharmacokinetics were compared in a randomized clinical trial in Thailand among patients with malaria and healthy volunteers. A single oral dose of 1500 mg mefloquine hydrochloride was administered to 11 patients and 5 volunteers and 750 mg was given to 16 patients and 5 volunteers. Efficacy was 82% for 1500 mg and 63% for 750 mg. In cured patients taking 750 mg mefloquine, peak plasma drug concentration (Cmax) and area under the plasma concentration-time curve (AUC) were significantly greater than in the patients for whom treatment failed (p less than 0.0005 and p less than 0.01, respectively), and plasma mefloquine levels were significantly higher from 8 hours to 18 days after treatment. Mefloquine AUC was reduced and variable in the presence of diarrhea. Compared with noninfected volunteers, clinically ill patients displayed a delayed time to reach peak concentration (p less than 0.01) and significantly higher mefloquine plasma levels in the first 2 days after administration of either the 750 mg or the 1500 mg dose. Mefloquine AUC was similar in patients with malaria and healthy volunteers. Because plasma levels increased in temporal relationship with clinical illness, mefloquine volume of distribution or clearance (or both) was reduced during the acute phase of illness.
Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Animals; Drug Tolerance; Humans; Malaria; Male; Mefloquine; Plasmodium falciparum; Reference Values
PubMed: 2225700
DOI: 10.1038/clpt.1990.168 -
Angewandte Chemie (International Ed. in... Jun 2013The controversy over the absolute configuration of (+)-erythro-mefloquine, the less psychosis-causing enantiomer of the anti-malarial drug Lariam, has been resolved by...
The controversy over the absolute configuration of (+)-erythro-mefloquine, the less psychosis-causing enantiomer of the anti-malarial drug Lariam, has been resolved by Mosher ester crystallization. The configuration determined previously by physical methods is correct, whereas the configuration determined by three enantioselective syntheses is wrong.
Topics: Antimalarials; Erythromycin; Mefloquine; Stereoisomerism
PubMed: 23616269
DOI: 10.1002/anie.201300258 -
Lancet (London, England) Aug 1992
Topics: Abnormalities, Drug-Induced; Adult; Female; Humans; Malaria; Mefloquine; Pregnancy; Travel
PubMed: 1353223
DOI: 10.1016/0140-6736(92)92403-3 -
European Journal of Clinical... 1997To assess the effect of food on the pharmacokinetics of the antimalarial mefloquine and its major plasma metabolite in healthy volunteers. (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
OBJECTIVES
To assess the effect of food on the pharmacokinetics of the antimalarial mefloquine and its major plasma metabolite in healthy volunteers.
METHODS
In an open, two-way cross-over study, 20 healthy male volunteers who had fasted overnight were randomised to receive a single oral dose of 750 mg mefloquine in the absence or presence of a standardised, high-fat breakfast, administered 30 min before drug administration. Blood samples were taken at specific times over an 8-week period. Plasma concentrations of mefloquine and its carboxylic acid metabolite were determined by high-performance liquid chromatography for pharmacokinetic evaluation.
RESULTS
The parameters Cmax and AUC of both mefloquine and its metabolite were significantly (P < 0.05) higher under post-prandial conditions than under fasting conditions (mefloquine: mean Cmax 1500 vs 868 micrograms.l-1, mean AUC 645 vs 461 mg l-1.h; metabolite: Cmax 1662 vs 1231 micrograms.l-1, AUC 1740 vs 1310 mg l-1.h). The intersubject variability in Cmax and AUC of mefloquine was less than 30% (coefficient of variation). The time to peak plasma concentration of mefloquine was significantly shorter after food intake (17 vs 36 h). Compared with absorption in volunteers who had fasted, food did not alter t1/2 (mefloquine and its metabolite) and tmax (metabolite).
CONCLUSION
Under the conditions of this study, food increases the rate and the extent of mefloquine absorption. It is reasonable to recommend that mefloquine be administered with food in travellers receiving chemoprophylaxis and in patients on recovery receiving curative treatment. In acutely ill patients, mefloquine should be taken as soon as possible and administration with or shortly after meals should be attempted as soon as feasible.
Topics: Administration, Oral; Adult; Antimalarials; Area Under Curve; Biological Availability; Cross-Over Studies; Food; Half-Life; Humans; Intestinal Absorption; Male; Mefloquine
PubMed: 9403285
DOI: 10.1007/s002280050351 -
Lancet (London, England) Apr 1993The spread of chloroquine-resistant Plasmodium falciparum malaria has led to increased use of mefloquine prophylaxis by US Peace Corps volunteers in sub-Saharan Africa.... (Clinical Trial)
Clinical Trial Comparative Study
The spread of chloroquine-resistant Plasmodium falciparum malaria has led to increased use of mefloquine prophylaxis by US Peace Corps volunteers in sub-Saharan Africa. We compared long-term mefloquine with other drug regimens for effectiveness and tolerance. The incidence of Plasmodium falciparum infections and of adverse reactions was compared in Peace Corps volunteers who took chloroquine weekly, mefloquine weekly, mefloquine every other week, or weekly chloroquine plus daily proguanil. Weekly mefloquine was 94% more effective than chloroquine (95% CI 86% to 97%), 86% more effective than chloroquine plus proguanil (95% CI 67% to 94%), and 82% more effective than prophylaxis with mefloquine when taken every other week (95% CI 68% to 90%). No serious adverse reactions were observed. Mild adverse events were equally frequent in mefloquine users and chloroquine users, and the frequency of these events declined with increasing duration of prophylaxis. Mefloquine is an effective and well-tolerated drug for prophylaxis of malaria by short-term and long-term travellers.
Topics: Africa, Western; Chloroquine; Cohort Studies; Drug Administration Schedule; Drug Therapy, Combination; Humans; Long-Term Care; Malaria, Falciparum; Mefloquine; Proguanil
PubMed: 8096560
DOI: 10.1016/0140-6736(93)93058-9 -
Malaria Journal Aug 2009Mefloquine has historically been considered safe and well-tolerated for long-term malaria chemoprophylaxis, but prescribing it requires careful attention in order to...
BACKGROUND
Mefloquine has historically been considered safe and well-tolerated for long-term malaria chemoprophylaxis, but prescribing it requires careful attention in order to rule out contraindications to its use. Contraindications include a history of certain neurological conditions that might increase the risk of seizure and other adverse events. The precise pathophysiological mechanism by which mefloquine might predispose those with such a history to seizure remains unclear.
PRESENTATION OF THE HYPOTHESIS
Studies have demonstrated that mefloquine at doses consistent with chemoprophylaxis accumulates at high levels in brain tissue, which results in altered neuronal calcium homeostasis, altered gap-junction functioning, and contributes to neuronal cell death. This paper reviews the scientific evidence associating mefloquine with alterations in neuronal function, and it suggests the novel hypothesis that among those with the prevalent EPM1 mutation, inherited and mefloquine-induced impairments in neuronal physiologic safeguards might increase risk of GABAergic seizure during mefloquine chemoprophylaxis.
TESTING AND IMPLICATIONS OF THE HYPOTHESIS
Consistent with case reports of tonic-clonic seizures occurring during mefloquine chemoprophylaxis among those with family histories of epilepsy, it is proposed here that a new contraindication to mefloquine use be recognized for people with EPM1 mutation and for those with a personal history of myoclonus or ataxia, or a family history of degenerative neurologic disorder consistent with EPM1. Recommendations and directions for future research are presented.
Topics: Antimalarials; Humans; Mefloquine; Seizures
PubMed: 19656408
DOI: 10.1186/1475-2875-8-188