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 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasmodium falciparum malaria in Thailand is resistant to available antimalarial drugs, which necessitates the search for alternative drugs. In a clinical trial mefloquine 1250 mg in divided doses was compared with oral artemether at 700 mg total dose given over 5 days in acute uncomplicated falciparum malaria. 46 adult men, aged 15-50 years and weighing 45-65 kg, with acute uncomplicated falciparum malaria, no history of liver or kidney diseases, and not history of tasking antimalarials for this episode of illness were recruited at the Bangkok Hospitak for Tropical Diseases. 12 were treated with mefloquine and 34 with oral artemether. Hospital follow-up was 28 days for the artemether group and 42 days for the mefloquine group. Parasites did not clear from the blood of 2 patients in the mefloquine group, although there was a decrease in parasitemia. The other 10 patients in the mefloquine group has a good initial response with mean parasite clearance times and fever clearance times of 64 and 27 hours respectively. Oral artemether gave a significantly faster parasite clearance time than mefloquine (30 vs. 64 hours), 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 with 600 mg intramuscular artemether given over 5 days. Mefloquine 1250 mg has a cure rate of 80-84% but it produces side effects such as vomiting. The treatment with artemether should last at least 5 days with a dose above 600 mg for a cure rate approaching 100%. This treatment is still likely to be more acceptable to patients than the combination regimen of quinine plus tetracycline for 7 days. These findings suggest that neither artemether nor mefloquine is effective against the intrahepatic stage of Plasmodium vivax. Primaquine is the choice of drug for radical cure.
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PMID:Comparison of oral artemether and mefloquine in acute uncomplicated falciparum malaria. 135 18

The pharmacokinetics of mefloquine at the therapeutic dose of 750 mg single orally were compared between cured and recrudescent patients with acute uncomplicated falciparum malaria. Mefloquine was well-tolerated during the study. The side-effects found were nausea, vomiting and diarrhea. Five patients showed R-I and two showed R-II types of response. All recrudescent patients came from the eastern border of Thailand. The time taken to clear the parasites (PCT) was significantly longer in patients with recrudescence (99.6 +/- 36.9 and 63.0 +/- 8.9 hours); however, there was no difference regarding fever clearance time (FCT: 39.0 +/- 16.1 and 31.0 +/- 21.3 hours). The maximum concentration (Cmax) and the concentration on the first and second days in cured patients were significantly higher than those of treatment failure patients. Other pharmacokinetic parameters appeared to be similar in both groups. The present study indicates the existence of mefloquine-resistant falciparum malaria in the eastern border of Thailand. Inadequate mefloquine concentration may play an important role in this aspect. In addition, this study also suggests that Cmax or the concentrations on the first or second day of treatment may be used as guidelines to predict the outcome of treatment.
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PMID:Pharmacokinetics of mefloquine in treatment failure. 182 Jun 38

At the Department of Communicable and Tropical Diseases, Rigshospitalet, Denmark, mefloquine has been used since 1982 for the treatment of patients with suspected or verified chloroquine and sulfadoxine-pyrimethamine resistant P. falciparum malaria. Eighty-one patients treated with mefloquine are reviewed. Forty patients had complicated malaria; 18 were initially treated with IV quinine. Mefloquine dose for adults was 1,500 mg in one dose or divided in two with six hourly intervals. Mild gastrointestinal side effects were common; in 10 patients, the medication had to be repeated because of vomiting. No neurological or neuropsychiatric side effects were recorded in relation to treatment or during the follow up period (30 days). Temperature subsided with a mean of 2.7 days after initiation of treatment and trophozoites cleared with a mean of 3.6 days. One patient had recrudescence. Mefloquine is found safe and effective for the treatment of P. falciparum malaria and is recommended for treatment of worldwide acquired P. falciparum malaria, although patients should be monitored closely to disclose resistance.
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PMID:Treatment of Plasmodium falciparum malaria with mefloquine alone or in combination with i.v. quinine at the Department of Communicable and Tropical Diseases, Rigshospitalet, Copenhagen 1982-1988. 207 60

Two randomised double-blind trials were conducted to examine the activity and tolerability of mefloquine alone and in combination with sulfadoxine/pyrimethamine (MSP). In one trial mefloquine was compared with chloroquine in 40 patients with Plasmodium vivax malaria and in the other one mefloquine was compared with MSP in 40 patients with P falciparum malaria. The former trial showed that both a single oral dose of 250 mg mefloquine and a single oral dose of 450 mg chloroquine (base) were highly effective in relieving symptoms of malaria and in clearing P vivax parasitaemia. No side-effects and no changes in laboratory variables attributable to the test drugs were observed. The other trial showed that a single oral dose of 750 mg mefloquine and a single oral dose of MSP (750 mg mefloquine plus 3 tablets of 'Fansidar', were equally effective in the treatment of falciparum malaria. 2/4 treatment failures in the mefloquine group and 2/3 treatment failures in the MSP group were due to low plasma drug levels resulting from vomiting soon after ingestion of the tablets. Gametocytes of P falciparum were unaffected by either mefloquine or MSP. 5 patients in each group had side-effects such as vomiting, skin rash, diarrhoea, and transient mental confusion. Mefloquine was well tolerated by patients with glucose-6-phosphate dehydrogenase deficiency or heterozygous haemoglobin E.
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PMID:Trials of mefloquine in vivax and of mefloquine plus 'fansidar' in falciparum malaria. 285 43

Halofantrine (WR 171,669) hydrochloride was administered orally to 82 patients infected with Plasmodium falciparum malaria on the Thai-Kampuchean border between June 1982 and December 1983 in a randomized double-blind treatment trial which compared the efficacy of halofantrine with that of mefloquine. Halofantrine was curative with oral treatment on a single day in 65% of patients (13/20) who received 1000 mg followed 6 hours later by an additional 500 mg, and in 88% of patients (53/60) who received 500 mg every 6 hours for 3 doses. Mefloquine was curative in 88% of patients (22/25) given a single oral dose of 1000 mg and in 97% of patients (38/39) given a single oral dose of 1500 mg. The difference in cure rates between the 3-dose halofantrine regimen and either of the mefloquine regimens was not significant. The mean parasite clearance time for all regimens ranged from 75 to 84 hours. The mean fever clearance time for all four treatment groups was in the range 50-60 hours, with no significant differences between groups. Post-dosing side-effects in patients treated with halofantrine consisted of nausea, vomiting, abdominal pain and diarrhoea and were not significantly different from those treated with mefloquine. Halofantrine therefore appeared to be of comparable efficacy to mefloquine in the treatment of multidrug-resistant P. falciparum malaria.
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PMID:Malaria: treatment efficacy of halofantrine (WR 171,669) in initial field trials in Thailand. 329 28

A double-blind, randomized, dose-finding, phase II mefloquine trial was carried out in 147 adult male patients suffering from acute, uncomplicated, falciparum malaria and admitted to the Hospital for Tropical Diseases, Bangkok, between January 1980 and April 1981. Mefloquine was administered as a single oral dose of 500, 750, or 1000 mg (base) in the form of the hydrochloride. The clinical and parasitological responses were satisfactory with all three dosage regimens. The cure rates for the 1000-, 750-, and 500-mg doses were 100%, 92.5%, and 95% respectively, over an observation period of 63 days.The side-effects, which were transient and generally mild, included nausea, vomiting, and diarrhoea. No significant changes were noted in haematological or biochemical parameters in any of the three groups. Sinus bradycardia, which started 4-7 days after drug administration and lasted for a few weeks, was seen in 10 patients. It was symptomless and needed no treatment.Acute brain syndrome was observed in one patient on day 21 after receiving a 1000-mg dose of mefloquine.Mefloquine was well tolerated in one case of acute renal failure, in 10 cases of moderately severe malaria with jaundice, in 13 cases with glucose-6-phosphate dehydrogenase deficiency, and in one case of thalassaemia.Mefloquine showed no effect on either gametocytes of Plasmodium falciparum or tissue forms of P. vivax.Mefloquine hydrochloride was found to be an effective drug for the treatment of falciparum malaria and tended to produce a more rapid clinical and parasitological response at the highest tested dose of 1000 mg (base).
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PMID:A phase II clinical trial of mefloquine in patients with chloroquine-resistant falciparum malaria in Thailand. 634 13

Mefloquine was compared with sulfadoxine-pyrimethamine for safety and efficacy in a randomized, double-blind clinical trial in adult males from a malaria-endemic area of Brazil. A total of 99 oligosymptomatic and symptomatic volunteers with Plasmodium falciparum parasitaemia took part in the trial; 49 were given 1000 mg of mefloquine and the remainder received 1500 mg of sulfadoxine plus 75 mg of pyrimethamine, in a single oral dose.Mefloquine was 100% successful in clearing parasitaemia within 7 days; there were no recrudescences. Sulfadoxine-pyrimethamine was less successful; 35 cases showed an S-type response, 8 an RI response, 3 an RII, and 2 an RIII response. The side-effects of mefloquine were mild and transient and included headache, nausea, vomiting, dizziness, and diarrhoea. A satisfactory weight gain and rise in haemoglobin level were seen in both groups.
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PMID:A phase II clinical trial of mefloquine in Brazilian male subjects. 636 Apr 1

Mefloquine is an orally administered blood schizontocide. Initial dose-finding and comparative studies performed between 1977 and 1989 demonstrated efficacy of mefloquine as prophylaxis in nonimmune individuals and in the suppression and treatment of malaria in adults and children caused by multidrug-resistant Plasmodium falciparum. It was also effective against P. vivax infection, while data concerning the treatment of P. ovale and P. malariae infections were limited. In an attempt to delay the emergence of resistance to this promising antimalarial agent, mefloquine was combined with sulfadoxine and pyrimethamine. Although initial clinical trials indicated that this regimen was effective in preventing and treating falciparum malaria, recent treatment failures, the potential for severe dermatological reactions and lack of therapeutic advantage over mefloquine alone has prompted the World Health Organization to recommended that the combination be no longer used for treatment or prophylaxis of malaria. Mefloquine is generally well tolerated in both adults and children, with nausea, vomiting, diarrhoea, headache, dizziness, rash, pruritus and abdominal pain being the most common adverse effects, although it is difficult to distinguish between disease- and treatment-related events. The incidence of these adverse effects is similar to or lower than those observed with other antimalarial agents. Cardiovascular changes, such as bradycardia, occasionally occur. The most notable adverse effects associated with mefloquine are neuropsychiatric disturbances; precipitation of such events should be closely monitored and requires termination of prophylaxis or therapy. The eventual emergence of resistance to mefloquine, as with many other antimalarial agents, was inevitable. Mefloquine resistance is established in certain areas of Thailand and may be becoming a growing problem in other regions of the world. In order to preserve the efficacy of mefloquine in non-resistant areas, this useful agent should be used with care and only prescribed for prophylaxis in travellers and treatment in areas of multidrug-resistant plasmodia. Future options to combat mefloquine resistance may include the combination of mefloquine with other antimalarial agents such as qinghaosu derivatives. Thus, with cautious use and possible combination with other agents, mefloquine is likely to remain an important treatment option for falciparum malaria, a widespread parasitic disease for which an increasing number of drugs have proved inadequate.
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PMID:Mefloquine. A review of its antimalarial activity, pharmacokinetic properties and therapeutic efficacy. 768 11

Malaria remains a major public health problem in large areas of the world. One of the major factors responsible for the resurgence is the emergence of Plasmodium falciparum, resistant to available antimalarials. An antimalarial, mefloquine, has been considered since its introduction as a promising alternative antimalarial drug to overcome the situation of widespread multidrug resistant P falciparum. Pharmacokinetic studies of mefloquine have been investigated in several groups of subjects either as mefloquine alone or as combined regimens. The oral absorption of mefloquine is relatively rapid, reaching peak concentrations within 24 hours. Metabolism takes place in the liver, with carboxymefloquine as a major metabolite. Mefloquine has a large apparent volume of distribution of 200 L and is highly bound (98%) to plasma proteins. The elimination is slow; the terminal half-life is 13 10 to 14 days in Thai patients with falciparum malaria. Vomiting within 1 hour of drug administration has an influence on blood concentrations of mefloquine and this may result in treatment failure. The whole blood concentrations of mefloquine on the first two days of treatment are important determinants of parasitological response. There appear to be no pharmacokinetic interactions between mefloquine and the other two components of Fansimef in patients with uncomplicated falciparum malaria. The advantage of this combination over mefloquine alone in multidrug resistant P falciparum is still debatable. However, recent data seem to support the higher efficacy of Fansimef over mefloquine alone. Concurrent administration of antibiotics, ie ampicillin and tetracycline with mefloquine results in a significant increase in maximum concentration, reduction of the apparent volume of distribution and shortening of the terminal elimination half-life of mefloquine. An antiemetic drug metoclopramide accelerates the absorption of mefloquine and increases the maximum concentration. In contrast, mefloquine concentrations are decreased in the presence of an antimalarial, artesunate. Primaquine has no effect on the pharmacokinetics of mefloquine when given concurrently.
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PMID:Clinical application of mefloquine pharmacokinetics in the treatment of P falciparum malaria. 772 Dec 26

Plasmodium falciparum in south-east Asia is highly resistant to chloroquine and sulfadoxine-pyrimethamine. Mefloquine used to be the chemosuppressant drug of choice in areas with chloroquine resistance. However, sensitivity to this drug has recently decreased in Thailand, Cambodia and Myanmar, and there is no suitable single alternative drug. We therefore investigated possible alternative combination therapies for multidrug resistant falciparum malaria. 120 male Thai patients at Makarm Malaria Clinic, Chantaburi, in eastern Thailand were allocated at random to receive either oral artemether (group A) or artesunate (group B) at a single dose of 300 mg on day 1, both followed by mefloquine, 750 and 500 mg at 24 and 30 h, respectively. Follow-up was on days 1, 2, 7, 14, 21, 28, 35 and 42. Patients in both groups had a rapid initial response to treatment; in most cases parasitaemia was cleared within 24 h, and fever was cleared within 24 h in 62% and 76.7% of the patients in groups A and B, respectively. 58 patients in group A and 57 in group B completed follow-up and cure rates were 98% and 97%, respectively. Reinfection could not be excluded for the 3 patients with recrudescences; all were cured with a repeated course of treatment. No serious adverse effect was observed in either group, only mild and transient nausea, vomiting and loss of appetite, with no significant difference between the 2 groups. These results suggest that a single oral dose of 300 mg of either artemether or artesunate followed by 1250 mg of mefloquine in 2 divided doses is effective against multiple drug resistant falciparum malaria. Either regimen can be considered as a suitable 'stand-by' in endemic areas of multiple drug resistant falciparum malaria.
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PMID:Artemether or artesunate followed by mefloquine as a possible treatment for multidrug resistant falciparum malaria. 888 93


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