title: Review: Improving the therapeutic index of 8-aminoquinolines by the use of drug combinations: review of the literature and proposal for future investigations.
abstract: Because 8-aminoquinolines affect critical survival stages of Plasmodium parasites, treatment and control of malaria could be markedly improved by more widespread use of these drugs; however, hemolytic toxicity, which is widely prevalent in G6PD-deficient patients, severely constrains this use. Primaquine was approved more than 50 years ago after extensive clinical testing. Review of the mid-20th century literature in the light of present understanding of pharmacokinetics and metabolism suggests that manipulation of these factors might dissociate 8-aminoquinoline efficacy from toxicity and lead to an improved therapeutic index.
authors.affiliation: Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA. Hya.yin.myint@us.army.mil
authors.forename: Hla Y
authors.initials: HY
authors.lastname: Myint
authors.forename: Jonathan
authors.initials: J
authors.lastname: Berman
authors.forename: Larry
authors.initials: L
authors.lastname: Walker
authors.forename: Brandon
authors.initials: B
authors.lastname: Pybus
authors.forename: Victor
authors.initials: V
authors.lastname: Melendez
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Baird
authors.forename: Colin
authors.initials: C
authors.lastname: Ohrt
mesh_terms: D000634:Aminoquinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000517:prevention & control; D010961:Plasmodium / Q000187:drug effects*; D011319:Primaquine / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D011319:Primaquine; C080436:8-aminoquinoline