Amodiaquine hydrochloride

Amodiaquine hydrochloride
INN
Drug class
Routes of administration	Oral
Pregnancy category
Bioavailability
Metabolism	Hepatic
Elimination half-life	3-12 hours
Excretion	Renal
Legal status
CAS Number	6398-98-7
PubChem	2165
DrugBank	DB00613
ChemSpider	2080
KEGG	D07450

Amodiaquine hydrochloride is an antimalarial medication used primarily for the treatment and prevention of malaria. It is a derivative of chloroquine and is often used in combination with other antimalarial agents to enhance efficacy and reduce the risk of resistance.

Pharmacology

Mechanism of Action

Amodiaquine hydrochloride works by interfering with the growth of Plasmodium parasites in the red blood cells of the human host. The exact mechanism is not fully understood, but it is believed to involve the inhibition of heme polymerase, an enzyme crucial for the detoxification of heme, which is toxic to the parasite.

Pharmacokinetics

Amodiaquine is rapidly absorbed from the gastrointestinal tract when administered orally. It undergoes extensive hepatic metabolism to its active metabolite, desethylamodiaquine. The drug and its metabolites are primarily excreted via the kidneys. The elimination half-life of amodiaquine is approximately 3 to 12 hours, while that of desethylamodiaquine is longer, contributing to its sustained antimalarial effect.

Clinical Use

Indications

Amodiaquine hydrochloride is indicated for the treatment of uncomplicated Plasmodium falciparum malaria. It is often used in combination with other antimalarials, such as artesunate, to form artemisinin-based combination therapies (ACTs), which are recommended by the World Health Organization for the treatment of malaria.

Dosage and Administration

The dosage of amodiaquine hydrochloride varies depending on the formulation and the combination with other drugs. It is typically administered orally, with the dose adjusted according to the patient's weight and the severity of the infection.

Adverse Effects

Common Side Effects

Common side effects of amodiaquine hydrochloride include gastrointestinal disturbances such as nausea, vomiting, and abdominal pain. Headache and dizziness are also frequently reported.

Serious Adverse Effects

Serious adverse effects include hepatotoxicity and agranulocytosis, which can be life-threatening. These effects are rare but necessitate careful monitoring of liver function and blood cell counts during treatment.

Contraindications

Amodiaquine hydrochloride is contraindicated in patients with a history of hypersensitivity to amodiaquine or related compounds. It should also be avoided in individuals with pre-existing liver disease or hematological disorders.

Drug Interactions

Amodiaquine may interact with other medications metabolized by the liver, potentially altering their efficacy or increasing the risk of adverse effects. Caution is advised when co-administering with other hepatotoxic drugs.

Resistance

Resistance to amodiaquine has been reported in some regions, primarily due to mutations in the Plasmodium falciparum genome. This has led to the development of combination therapies to mitigate resistance and improve treatment outcomes.

History

Amodiaquine was first synthesized in the 1940s and has been used extensively in the treatment of malaria. Its use has declined in some areas due to the emergence of resistance and the availability of newer antimalarial agents.

Research and Development

Ongoing research is focused on improving the efficacy and safety profile of amodiaquine through the development of new formulations and combination therapies. Studies are also investigating its potential use in the treatment of other parasitic infections.

See Also

• Malaria
• Chloroquine
• Artemisinin-based combination therapy

External Links

• [World Health Organization - Malaria]
• [Centers for Disease Control and Prevention - Malaria]