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

Islahudin, Farida, Pleass, Richard ORCID: https://orcid.org/0000-0001-7438-8296, Avery, Simon V and Ting, Kang-Nee (2012) 'Quinine interactions with tryptophan and tyrosine in malaria patients, and implications for quinine responses in the clinical setting.'. The Journal of Antimicrobial Chemotherapy, Vol 67, Issue 10, pp. 2501-2505.

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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.

Item Type: Article
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 256 Antimalarials
QV Pharmacology > QV 38 Drug action.
QX Parasitology > Protozoa > QX 135 Plasmodia
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 770 Therapy
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1093/jac/dks253
Depositing User: Mary Creegan
Date Deposited: 13 Feb 2013 18:06
Last Modified: 06 Feb 2018 13:05
URI: http://archive.lstmed.ac.uk/id/eprint/3268

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