Quinine interactions with tryptophan and tyrosine in malaria patients, and implications for quinine responses in the clinical setting

Farida Hanim Islahudin, Richard J. Pleass, Simon V. Avery, Kang Nee Ting

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objectives: Recent work with the yeast model revealed that the antiprotozoal drug quinine competes with tryptophan for uptake via a common transport protein, causing cellular tryptophan starvation. In the present work, it was hypothesized that similar interactions may occur in malaria patients receiving quinine therapy. Patients and methods: A direct observational study was conducted in which plasma levels of drug and amino acids (tryptophan, tyrosine and phenylalanine) were monitored during quinine treatment of malaria patients with Plasmodium falciparum infections. Results: Consistent with competition for uptake from plasma into cells, plasma tryptophan and tyrosine levels increased ≥2-fold during quinine therapy. Plasma quinine levels in individual plasma samples were significantly and positively correlated with tryptophan and tyrosine in the same samples. Control studies indicated no effect on phenylalanine. Chloroquine treatment of Plasmodium vivax-infected patients did not affect plasma tryptophan or tyrosine. During quinine treatment, plasma tryptophan was significantly lower (and quinine significantly higher) in patients experiencing adverse drug reactions. Conclusions: Plasma quinine levels during therapy are related to patient tryptophan and tyrosine levels, and these interactions can determine patient responses to quinine. The study also highlights the potential for extrapolating insights directly from the yeast model to human malaria patients.

Original languageEnglish
Article numberdks253
Pages (from-to)2501-2505
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume67
Issue number10
DOIs
Publication statusPublished - Oct 2012
Externally publishedYes

Fingerprint

Quinine
Tryptophan
Malaria
Tyrosine
Phenylalanine
Therapeutics
Yeasts
Plasmodium vivax
Chloroquine
Plasmodium falciparum
Starvation
Plasma Cells
Drug-Related Side Effects and Adverse Reactions
Pharmaceutical Preparations
Observational Studies
Carrier Proteins
Amino Acids

Keywords

  • Amino acid uptake
  • Antimalarial drugs
  • Antiparasitic drugs
  • Aromatic amino acids
  • Competitive inhibition

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Quinine interactions with tryptophan and tyrosine in malaria patients, and implications for quinine responses in the clinical setting. / Islahudin, Farida Hanim; Pleass, Richard J.; Avery, Simon V.; Ting, Kang Nee.

In: Journal of Antimicrobial Chemotherapy, Vol. 67, No. 10, dks253, 10.2012, p. 2501-2505.

Research output: Contribution to journalArticle

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