title: Primaquine pharmacology in the context of CYP 2D6 pharmacogenomics: Current state of the art.
abstract: Primaquine is the only antimalarial drug available to clinicians for the treatment of relapsing forms of malaria. Primaquine development and usage dates back to the 1940s and has been administered to millions of individuals to treat and eliminate malaria infections. Primaquine therapy is not without disadvantages, however, as it can cause life threatening hemolysis in humans with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In addition, the efficacy of primaquine against relapsing malaria was recently linked to CYP 2D6 mediated activation to an active metabolite, the structure of which has escaped definitive identification for over 75years. CYP 2D6 is highly polymorphic among various human populations adding further complexity to a comprehensive understanding of primaquine pharmacology. This review aims to discuss primaquine pharmacology in the context of state of the art understanding of CYP 2D6 mediated 8-aminoquinoline metabolic activation, and shed light on the current knowledge gaps of 8-aminoquinoline mechanistic understanding against relapsing malaria.
authors.affiliation: Military Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD 20910, USA. Electronic address: sean.r.marcsisin.mil@mail.mil.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Marcsisin
authors.affiliation: Military Malaria Research Program, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD 20910, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Reichard
authors.affiliation: Department of Pathology, Dwight D. Eisenhower Army Medical Center, FT. Gordon, GA 30905, USA.
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Pybus
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D055432:Metabolomics; D011110:Polymorphism, Genetic; D011319:Primaquine / Q000009:adverse effects / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011355:Prodrugs / Q000009:adverse effects / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D011355:Prodrugs; D019389:Cytochrome P-450 CYP2D6; D011319:Primaquine
keywords: 8-Aminoquinoline; CYP 2D6; Hepatic metabolism; Pharmacogenomics; Plasmodium vivax; Primaquine