The Journal of tropical medicine and hygiene 2011-12-01

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

Hla Y Myint, Jonathan Berman, Larry Walker, Brandon Pybus, Victor Melendez, J Kevin Baird, Colin Ohrt

Index: Am. J. Trop. Med. Hyg. 85(6) , 1010-4, (2011)

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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.