Mefloquine Dihydroartemisinin

Knowledge of local resistance patterns is important to determine the treatment regimen. There is increasing chloroquine and pyrimethamine-sulfado-xine (Fansidar) resistance in Africa and in some areas at the border of Thailand there is resistance for almost all antimalarial drugs including halofantrine, mefloquine and quinine. In these areas only the artemisinin derivatives (artemether, arteether, arte-sunate, dihydroartemisinin) are effective. 

Three currently-used artemisinin based combination therapies (ACT) artesunate-mefloquine, artemether-lumefantrine and dihydroartemisinin-piperaquine, have been proven highly simple, safe and effective in the treatment of multidrug resistant P. falciparum malaria. 

Pinheiro, J.C., Ferreira, M.M.C. and Romero, O.A.S. (2001) Antimalarial activity of dihydroartemisinin derivatives against P. falciparum resistant to mefloquine a quantum chemical and multivariate study. J. Mol. Struct. (Theochem), 572, 35—44. 

Ethers, esters and carbonates of dihydroartemisinin have been prepared to obtain novel and more active derivatives [45]. After examination of the ethers, including the epimers at position 10, artemether (31 2, R = CH3) and arteether (31 3, R = CH2CH3), they were found to be about twice as active as artemisinin, but less active than dihydroartemisinin. Artemether has been isolated as a natural constituent of A. annua. Arteether was found to be 34 times more active than chloroquine against the W-2 (Indochina) clone of P. falciparum (normally resistant to chloroquine) and three times less active against the D-6 (Sierra Leone) clone (normally resistant to mefloquine). Artemether was two times more active and eight times more active than mefloquine against the W-2 and D-6 clones, respectively. Both artemether and arteether are more oil soluble than artemisinin and are currently in clinical trials. 

Artemether pretreatment appears to modestly reduce mefloquine levels, whereas artemisinin and dihydroartemisinin do not affect the pharmacokinetics of mefloquine. If mefloquine is given shortly after artesunate its levels are lowered, but giving mefloquine two days in to artesunate treatment appears to raise mefloquine levels. The combined use of mefloquine with artemisinin derivatives might improve antimalarial activity. See also Co-artemeth-er + Mefloquine , p.224... 

Na-Bangchang K, Tippawangl )solP, Thanavibul A, Ubalee R, Karbwai J. Fbannaccddnetic and phaimac(xlynamic interacticns of mefloquine and dihydroartemisinin IntJ Clin Pharmacol Res ( 999) 19, 9-17. 

A series of artemisinin-based semisynthetic antimalarial derivatives, with all of them maintaining the key endoperoxide bridge, such as arteether (18), artemether (19), artesunate (20), and dihydroartemisinin (21), have been designed to improve the water solubility and the metabolic stability of artemisinin [53, 54], Among them, dihydroartemisinin (artenimol), is considered as a common active metaboUte of artemisinin derivatives [53, 54]. Currently, artemisinin-based therapies eombined with standard antimalarials such as amodiaquine, sulfadoxine-pyrimethamine, mefloquine, and lumefantrine are recommended by the World Health Organization (WHO) as first-line therapies for malaria [55, 56]. 

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