Quinine is derived from the bark of the cinchona tree, a traditional remedy for intermittent fevers from South America. The alkaloid quinine was purified in 1820 and has been used in the treatment and prevention of malaria since that time. Quinidine, the dextrorotatory stereoisomer of quinine, is at least as effective as parenteral quinine in the treatment of severe falciparum malaria. After oral administration, quinine is rapidly absorbed, reaches peak plasma levels in 1–3 hours, and is widely distributed in body tissues. The use of a loading dose in severe malaria allows the achievement of peak levels within a few hours. Individuals with malaria develop higher plasma levels of quinine than healthy controls, but toxicity is not increased, apparently because of increased protein binding. The half-life of quinine also is longer in those with severe malaria (18 hours) than in healthy controls (11 hours). Quinidine has a shorter half-life than quinine, mostly as a result of decreased protein binding. Quinine is primarily metabolized in the liver and excreted in the urine.
Quinine is a rapid-acting, highly effective blood schizonticide against the four species of human malaria parasites. The drug is gametocidal against P vivax and P ovale but not P falciparum. It is not active against liver stage parasites. The mechanism of action of quinine is unknown. Resistance to quinine is common in some areas of Southeast Asia, especially border areas of Thailand, where the drug may fail if used alone to treat falciparum malaria. However, quinine still provides at least a partial therapeutic effect in most patients.
1.
Parenteral treatment of severe falciparum malaria—For many years quinine dihydrochloride or quinidine gluconate were the treatments of choice for severe falciparum malaria, although intravenous artesunate is now preferred. Quinine can be administered slowly intravenously or, in a dilute solution, intramuscularly, but parenteral preparations are not available in the USA. Quinidine is available (although not always readily accessible) in the USA for the parenteral treatment of severe falciparum malaria. Quinidine can be administered in divided doses or by continuous intravenous infusion; treatment should begin with a loading dose to achieve effective plasma concentrations promptly. Because of its cardiac toxicity (see Chapter 14) and the relative unpredictability of its pharmacokinetics, intravenous quinidine should be administered slowly with cardiac monitoring. Therapy should be changed to an effective oral agent as soon as the patient has improved sufficiently.
2.
Oral treatment of falciparum malaria—Quinine sulfate is appropriate therapy for uncomplicated falciparum malaria except when the infection was transmitted in an area without documented chloroquine resistance. Quinine is commonly used with a second drug (most often doxycycline or, in children, clindamycin) to shorten the duration of use (usually to 3 days) and limit toxicity. Quinine is not generally used to treat nonfalciparum malaria.
3.
Malarial chemoprophylaxis—Quinine is not generally used in chemoprophylaxis owing to its toxicity, although a daily dose of 325 mg is effective.
4.
Babesiosis—Quinine is first-line therapy, in combination with clindamycin, in the treatment of infection with Babesia microti or other human babesial infections.