Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mefloquine has proved effective in chloroquine- and quinine-resistant falciparum malaria, but it cannot be given parenterally. We have measured the absorption of mefloquine hydrochloride suspension (mean 15.6, range 9.7-28.6 mg/kg) given by nasogastric tube to 19 cerebral malaria patients already receiving intravenous quinine. Absorption was rapid with both dose schedules used; mean absorption half-times were 1.5 and 1.8 hr, and plasma mefloquine concentrations exceeded 200 ng/g within 3 hr of completing administration in all but one exceptionally ill patient who died 40 hr later. Steady state plasma concentrations over 7 days ranged from 300 to 1,050 (mean 561) ng/g. Bioavailability of mefloquine suspension in cerebral malaria therefore appears to be adequate for treatment in all but the most severely ill patients. Although intragastric mefloquine cannot now be recommended as an alternative to intravenous quinine for the treatment of severe chloroquine-resistant falciparum malaria, this situation could change if quinine resistance increases further.
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PMID:Intragastric mefloquine is absorbed rapidly in patients with cerebral malaria. 387 57

Mefloquine, a new antimalarial which has been effective in curing malaria due to Plasmodium falciparum and P. vivax, was used for the first time in a patient infected with P. malariae. Treatment was successful, and the relatively long parasite clearance time and fever clearance time were probably characteristic of P. malariae rather than true drug resistance.
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PMID:Treatment of an acute case of Plasmodium malariae malaria with mefloquine. 634 73

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

The spread of multiresistant strains of Plasmodium falciparum in south-east Asia and South America and the appearance of chloroquine resistance in Africa indicates the urgent need for alternative drugs against these parasites. Mefloquine, a 4-quinoline methanol, is the only new drug that is currently at an advanced stage of development.Studies in animal models and in the clinic have shown that it is highly active as a blood schizontocide against strains that are resistant to many established antimalarials, e.g., chloroquine and pyrimethamine. It is not, however, effective as a causal prophylactic agent. Preclinical toxicological, teratological, and carcinogenicity studies do not indicate any major contraindications to its use.Intensive clinical studies have been carried out in Africa, North and South America, south-east Asia, and Europe. These studies have indicated that the compound is generally well tolerated, safe, and effective in the treatment of malaria, particularly infections with chloroquine-resistant parasites.In order to protect this new and promising drug against the development of resistance to it in endemic areas, it is important that its introduction should be accomplished in a rational and deliberate manner. Appropriate precautionary measures include the development of mefloquine combinations (a combination of mefloquine with pyrimethamine-sulfadoxine is presently under investigation), its use with primaquine as a gametocytocidal drug to prevent transmission, and its deployment primarily for treatment, being used for prophylaxis only in special risk groups.
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PMID:Development of mefloquine as an antimalarial drug. UNDP/World Bank/WHO update. 640 67

The new antimalarial drug mefloquine bound with high affinity (Kd approximately 3 X 10-7 M) to membrane lipids of normal mouse erythrocytes and of erythrocytes infected either with chloroquine-susceptible or chloroquine-resistant Plasmodium berghei. Approximately 80 nmol of mefloquine was bound per mg of total lipid. Mefloquine also bound to purified phospholipids with high affinity (Kd approximately 3 X 10-7 M). Phosphatidylinositol and phosphatidylserine bound 300 to 400 nmol of mefloquine per mg. Phosphatidylcholine and phosphatidylethanolamine bound approximately 100 nmol of mefloquine per mg. Mefloquine did not bind to hemoglobin with high affinity, but it bound to free ferriprotoporphyrin IX with a Kd of approximately 3 X 10-7 M. In comparison with mefloquine, chloroquine did not bind effectively to purified phospholipids, although it is known to bind with high affinity to free ferriprotoporphyrin IX. Greater binding to phospholipids may account for the superiority of mefloquine in the treatment of chloroquine-resistant malaria.
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PMID:The antimalarial drug mefloquine binds to membrane phospholipids. 697 9

Mefloquine hydrochloride (WR 142, 490) is a new investigational drug which is indicated for the prevention and treatment of cloroquine-resistant falciparum malaria thought to be resistant to other drugs. Available information on mefloquine, particularly its potential for "quinine-like" side effects, is of aeromedical importance. These side effects, if present, would be expected to alter performance and body physiology to a degree which would compromise flight safety. There is legitimate concern for mefloquine's safe use in aircrewmen. Mefloquine's potential for "quinine-like" side effects should be evaluated before it is routinely used for suppressive prophylaxis in aircrewmen.
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PMID:Aeromedical considerations of malaria prophylaxis with mefloquine hydrochloride. 698 45

The effect of various dosages of mefloquine hydrochloride (WR 142,490) and sulfadoxine-pyrimethamine in the suppression of malaria infections was studied in an area of northeastern Thailand highly endemic for both chloroquine-resistant Plasmodium falciparum and for P. vivax. Both preparations, in all regimens studied, were effective in greatly reducing the incidence of falciparum infections. Mefloquine was more active in preventing vivax parasitemia than sulfadoxine-pyrimethamine; however, this combination remains the commercially available regimen of choice where both parasites occur and P. falciparum is resistant to chloroquine.
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PMID:Chemosuppressive field trials in Thailand. IV. The suppression of Plasmodium falciparum and Plasmodium vivax parasitemias by mefloquine (WR 142,490, A 4-quinolinemethanol). 700 14

17 cases of resistant P. falciparum malaria are reported. They were observed in different populations: on one hand 9 Cambodian children refugees in France, on the other hand 8 French adults consulting after travels in South America or in South-East Asia. Different resistance levels to amino-4-quinolines and to a combination of sulfadoxine and pyrimethamine were found: they were more often from the RI type but sometimes from the RIII type also. 6 patients were treated with Mefloquine. Its activity was constant and rapid.
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PMID:[Drug resistance to malaria. Apropos of 17 cases in 2 years]. 702 70

At present the basic antimalarial drugs are still the 4-aminoquinolines chloroquine and amodiaquine, the combinations of antifol compounds (such as pyrimethamine and sulfadoxine = Fansidar), and quinine. In South East Asia and parts of Latin America Plasmodium falciparum has become highly resistant to chloroquine, and increasingly so to the antifol combinations. By selecting the antimalarials bearing the lowest risk of resistance, or combinations of them, an attempt can be made to avoid failures of treatment and chemoprophylaxis. The other areas endemic for malaria tropica may still be generally considered "chloroquine sensitive", although sporadic low-grade resistance to chloroquine is reported. It would be a mistake to replace chloroquine systematically by antifol combinations in those parts of the world now as well. The questions when drug resistance is to be suspected, and how individual treatment can be adjusted to it, are likewise discussed. Mefloquine is the best known new compound, with excellent activity against multiresistant Plasmodium falciparum. A combination with Fansidar is now being developed to prevent the former from inducing resistant strains. Despite considerable experimental advances a malaria vaccine is unlikely to be generally available before the end of this decade.
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PMID:[Current therapy and prevention of malaria and perspectives for the future]. 704 Dec 53


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