化合物信息

Drug Groups

approved

Description

An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [PubChem]

Indication

For the treatment of malaria and leg cramps

Pharmacology

Quinine is used parenterally to treat life-threatening infections caused by chloroquine-resistant Plasmodium falciparum malaria. Quinine acts as a blood schizonticide although it also has gametocytocidal activity against P. vivax and P. malariae. Because it is a weak base, it is concentrated in the food vacuoles of P. falciparum. It is thought to act by inhibiting heme polymerase, thereby allowing accumulation of its cytotoxic substrate, heme. As a schizonticidal drug, it is less effective and more toxic than chloroquine. However, it has a special place in the management of severe falciparum malaria in areas with known resistance to chloroquine.

Toxicity

Quinine is a documented causative agent of drug induced thrombocytopenia (DIT). Thrombocytopenia is a low amount of platelets in the blood. Quinine induces production of antibodies against glycoprotein (GP) Ib-IX complex in the majority of cases of DIT, or more rarely, the platelet-glycoprotein complex GPIIb-IIIa. Increased antibodies against these complexes increases platelet clearance, leading to the observed thrombocytopenia.

Affected Organisms

Biotransformation

Hepatic, over 80% metabolized by the liver.

Absorption

76 - 88%

Half Life

Approximately 18 hours

Protein Binding

Approximately 70%

Elimination

Quinine is eliminated primarily via hepatic biotransformation. Approximately 20% of quinine is excreted unchanged in urine.

Distribution

* 1.43 ± 0.18 L/kg [Healthy Pediatric Controls]
* 0.87 ± 0.12 L/kg [P. falciparum Malaria Pediatric Patients]
* 2.5 to 7.1 L/kg [healthy subjects who received a single oral 600 mg dose]

Clearance

* 0.17 L/h/kg [healthy]
* 0.09 L/h/kg [patients with uncomplicated malaria]
* 18.4 L/h [healthy adult subjects with administration of multiple-dose activated charcoal]
* 11.8 L/h [healthy adult subjects without administration of multiple-dose activated charcoal]
* Oral cl=0.06 L/h/kg [elderly subjects]

References

External Links