Artemether

Artemether is a semi-synthetic derivative of artemisinin, a natural product isolated from the plant Artemisia annua. It is used as an antimalarial agent and is a key component of artemisinin-based combination therapies (ACTs).

Mechanism and activity: Artemether acts quickly against malaria parasites, particularly Plasmodium falciparum, by generating reactive free radicals when the endoperoxide bridge encounters heme iron within the parasite. This leads to damage of parasite proteins and membranes. Its rapid action is balanced by the need for a longer-acting partner drug in combination therapy.

Clinical use: Artemether is most commonly formulated as artemether-lumefantrine, an oral ACT used for uncomplicated malaria. Other ACT combinations may include different partner drugs. For severe malaria, injectable artemether has been used in some settings, but artesunate is generally preferred for parenteral treatment. It is not recommended as monotherapy, because the short half-life of artemisinins can allow recrudescent infection and promote resistance if used alone.

Pharmacokinetics: Artemether is rapidly absorbed after oral administration, with bioavailability influenced by dietary fat. It is rapidly metabolized to dihydroartemisinin, an active metabolite, and is then cleared from the body through hepatic pathways and excretion.

Safety and resistance: Common adverse effects are generally mild and may include dizziness, headache, nausea, or vomiting. Serious adverse events are uncommon. Resistance to artemisinins has emerged in some regions when used improperly as monotherapy or with inadequate partner drugs; therefore ACTs are the standard approach to preserve efficacy.

Regulatory status: Artemether is listed in many national malaria control programs and is included in the World Health Organization's list of essential medicines as part of ACT regimens.