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  • Title: Review: Improving the therapeutic index of 8-aminoquinolines by the use of drug combinations: review of the literature and proposal for future investigations.
    Author: Myint HY, Berman J, Walker L, Pybus B, Melendez V, Baird JK, Ohrt C.
    Journal: Am J Trop Med Hyg; 2011 Dec; 85(6):1010-4. PubMed ID: 22144436.
    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.
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