MEFLOQUINE

개요Mefloquine, 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.

용도Labelled 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.