MEFLOQUINE

MEFLOQUINE C화학적 특성, 용도, 생산

개요

Mefloquine, which was synthesized with the intent of blocking the site of metabolism in quinine with the chemically stable CF3 group, exists as four optical isomers of nearly equal activity. The drug is active against chloroquine-resistant strains of plasmodium, yet cross-resistance is not uncommon. Metabolism is cited as the possible mechanism of resistance. Mefloquine is slowly metabolized through CYP3A4 oxidation to its major inactive metabolite, carboxymefloquine. Most of the parent drug is excreted unchanged into the urine. Its coadministration with CYP3A4 inhibitors (e.g., ketoconazole) has increased the area under the curve for mefloquine by inhibiting its metabolism to carboxymefloquine.

화학적 성질

Off-White Solid

용도

Labelled quinoline methanol antimalarial agent.
Mefloquine is also a 4-aminoquinoline. It is a blood schizonticide active against the asexual stages of all malaria parasites. Mefloquine is currently the prophylactic agent of choice for short-term travellers. Resistance of P. falciparum against mefloquine has occurred in South-East Asia. Only an oral formulation of mefloquine exists because of intense local irritation with parenteral use. It is well absorbed orally and notwithstanding a high protein binding of about 98% it is distributed throughout the body. Mefloquine is metabolized in the liver and eliminated slowly, mainly in bile and faeces with an elimination half-life of 10–30 days. Adverse effects include gastrointestinal pain and other disturbances and also, sinus bradycardia. More serious are CNS effects like dizziness and vertigo and more rarely neuropsychiatric disturbances, seizures.

Indications

Mefloquine (Lariam) is a 4-quinolinemethanol derivative used both prophylactically and acutely against resistant P. falciparum malaria. It is ineffective against the liver stage of P. vivax malaria.
While its detailed mechanism of action is unknown, it is an effective blood schizonticide; that is, it acts against the form of the parasite responsible for clinical symptoms. Orally administered mefloquine is well absorbed and has an absorption half-life of about 2 hours; the elimination half-life is 2 to 3 weeks. Among its side effects are vertigo, visual alterations, vomiting, and such CNS disturbances as psychosis, hallucinations, confusion, anxiety, and depression. It should not be used concurrently with compounds known to alter cardiac conduction or prophylactically in patients operating dangerous machinery. It should not used to treat severe malaria, as there is no intravenous formulation.

World Health Organization (WHO)

Mefloquine was developed in response to proliferation of multidrug resistant strains of Plasmodium falciparum, and has been widely used since the early 1980s. Provided the drug is used appropriately, the risks associated with its prophylactic use are clearly outweighed by the benefits. Mefloquine is listed in the WHO Model List of Essential Drugs.

Antimicrobial activity

Mefloquine is a lipophilic drug with a high affinity to membranes. A concentration of 10–40 nm has rapid dose-related activity against erythrocytic stages of Plasmodium spp., including strains resistant to chloroquine, sulfonamides and pyrimethamine. The C-11 (hydroxy) enantiomers have equal antimalarial activity. It also exhibits activity against bacteria (including methicillin-resistant Staphylococcus aureus), and some fungi and helminths.

원료

Resistance in P. falciparum is widespread in South East Asia where high-grade resistance was found in 15% of patients and low-grade resistance in about 50%. There is cross-resistance with quinine and halofantrine, and an inverse relationship with chloroquine resistance has been reported. The molecular basis of resistance remains unclear but polymorphisms of the pfmdr1 gene, associated with chloroquine resistance, led to increased sensitivity to mefloquine. Resistant strains of P. falciparum appeared in Africa before the drug was used in that continent, perhaps because of quinine abuse or intrinsic resistance. In South East Asia, declining response rates to combination therapy with mefloquine and artesunate are reported.

Pharmaceutical Applications

A synthetic 4-quinolinemethanol, formulated as the hydrochloride for oral administration. It is slightly soluble in water.

Pharmacokinetics

Oral absorption: 70–80%
C_max 1 g oral: 1 mg/L after 2–12 h
Plasma half-life: 20 days
Volume of distribution: 16–25 L/kg
Plasma protein binding: 98%
Mefloquine is concentrated two- to five-fold in erythrocytes. The major metabolites do not have antimalarial activity. Pregnant women require larger doses than non-pregnant women to achieve comparable blood levels. It is predominantly excreted in the bile. Less than 10% is excreted in urine.

Clinical Use

Antimalarial prophylaxis in areas of chloroquine resistance
Treatment of uncomplicated multidrug-resistant malaria
A mefloquine–artesunate co-formulation is available. Mefloquine has been used for the treatment of cutaneous leishmaniasis in South America.

부작용

At prophylactic doses risks of serious toxicity are about 1 in 10 000, similar to chloroquine. Doses used in therapy are more commonly associated with nausea, dizziness, fatigue, mental confusion and sleep loss. Psychosis, encephalopathy and convulsions are seen in about 1 in 1200–1700 patients. Mefloquine(+), the enantiomer with potential lower toxicity, is currently in development.

MEFLOQUINE 준비 용품 및 원자재

원자재

준비 용품

MEFLOQUINE 공급 업체

공급자	전화	이메일	국가	제품 수	이점
CONIER CHEM AND PHARMA LIMITED	+8618523575427	sales@conier.com	China	49390	58
Shaanxi Dideu Medichem Co. Ltd	+86-29-87569266 15319487004	1015@dideu.com	China	2263	58
TargetMol Chemicals Inc.	+1-781-999-5354 +1-00000000000	marketing@targetmol.com	United States	19892	58
Shanxi Xuanran Import and Export Trade Co., Ltd.	+8617735180244	mike_yan@xuanranglobal.com	CHINA	4022	58
Dideu Industries Group Limited	+86-29-89586680 +86-15129568250	1026@dideu.com	China	29220	58
Baoji Guokang Bio-Technology Co., Ltd.	0917-3909592 13892490616	gksales1@gk-bio.com	China	9339	58
Baoji Guokang Healthchem co.,ltd	+8615604608665 15604608665	dominicguo@gk-bio.com	CHINA	9427	58
Hangzhou MolCore BioPharmatech Co.,Ltd.	+86-057181025280; +8617767106207	sales@molcore.com	China	49739	58
Guangzhou Biocar Biotechnology Co.,Ltd.	+86-13397196830	carrie@gzbiocar.cn	China	436	58
Chemvon Biotechnology Co., Ltd	021-50790412	info@chemvon.com	China	371	57

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