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Am J Trop Med Hyg. 2011 Dec;85(6):1010-4. doi: 10.4269/ajtmh.2011.11-0498.

Review: Improving the therapeutic index of 8-aminoquinolines by the use of drug combinations: review of the literature and proposal for future investigations.

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1
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA. Hya.yin.myint@us.army.mil

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.

PMID:
22144436
PMCID:
PMC3225144
DOI:
10.4269/ajtmh.2011.11-0498
[Indexed for MEDLINE]
Free PMC Article
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