title: Quinine interactions with tryptophan and tyrosine in malaria patients, and implications for quinine responses in the clinical setting.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: School of Pharmacy, University of Nottingham Malaysia Campus, 43500 Semenyih, Malaysia.
authors: Farida
authors: F
authors: Islahudin
authors: Richard J
authors: RJ
authors: Pleass
authors: Simon V
authors: SV
authors: Avery
authors: Kang-Nee
authors: KN
authors: Ting
mesh_terms: D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000008:administration & dosage* / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D016780:Malaria, Vivax / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D011803:Quinine / Q000008:administration & dosage* / Q000494:pharmacology; D014364:Tryptophan / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014443:Tyrosine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000962:Antimalarials; D014443:Tyrosine; D014364:Tryptophan; D011803:Quinine