Quinine (DB00468): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Quinine, a cinchona alkaloid identified by DrugBank ID DB00468 and CAS Number 130-95-0, represents a compound of profound historical significance and complex contemporary clinical relevance. Originally derived from the bark of the South American cinchona tree, its isolation in 1820 and subsequent use marked the first successful application of a chemical agent to combat an infectious disease, fundamentally altering the course of global health and geopolitics. While historically employed for a range of ailments, its therapeutic role in modern medicine has been sharply curtailed by a narrow therapeutic index and a well-documented profile of severe, sometimes fatal, toxicities.

The primary mechanism of its antimalarial action involves the disruption of the Plasmodium parasite's heme detoxification pathway, leading to the accumulation of cytotoxic heme within the parasite's food vacuole. Its pharmacokinetic profile is notably complex, as its absorption, distribution, and clearance are dynamically altered by the acute malarial state it is used to treat.

Currently, the sole indication for quinine sulfate approved by the U.S. Food and Drug Administration (FDA) is the treatment of uncomplicated Plasmodium falciparum malaria. Its use in babesiosis, in combination with clindamycin, represents another important therapeutic application. However, the legacy of its widespread, unapproved off-label use for nocturnal leg cramps has prompted stringent regulatory actions, including an FDA Boxed Warning. This warning highlights the risk of life-threatening hematologic reactions, such as thrombocytopenia and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP), and unequivocally states that the risks of such use far outweigh any potential benefits.