Review: Improving the Therapeutic Index of 8-Aminoquinolines by the Use of Drug Combinations: Review of the Literature and Proposal for Future Investigations

Authors

• Hla Y. Myint, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MDFollow
• Jonathan Berman, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MDFollow
• Larry Walker, Department of Pharmacology and National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MSFollow
• Brandon Pybus, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MDFollow
• Victor Melendez, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MDFollow
• J. Kevin Baird, Eijkman–Oxford Clinical Research Unit, Jalan Diponegoro No. 69, Jakarta, IndonesiaFollow
• Colin Ohrt, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MDFollow

Date of this Version

2011

Citation

Am. J. Trop. Med. Hyg., 85(6), 2011, pp. 1010–1014

Comments

Copyright © 2011 by The American Society of Tropical Medicine and Hygiene

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.