METHODS: Six healthy male Malaysian subjects were given a single oral dose of 200 mg artemether. Blood samples were collected to 72 h. Plasma concentrations of the two compounds were measured simultaneously by reversed-phase h.p.l.c. with electro-chemical detection in the reductive mode.

RESULTS: Mean (+/- s.d.) maximum concentrations of ARM, 310 +/- 153 micrograms l-1, were reached 1.88 +/- 0.21 h after drug intake. The mean elimination half-life was 2.00 +/- 0.59 h, and the mean AUC 671 +/- 271 micrograms l-1 h. The mean Cmax of DHA, 273 +/- 64 micrograms l-1 was observed at 1.92 +/- 0.13 h. The mean AUC of DHA was 753 +/- 233 micrograms h l-1'. ARM and DHA were stable at < or = -20 degrees C for at least 4 months in plasma samples.

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.