epicinchonine and Malaria--Falciparum

Pharmacokinetics of quinine, quinidine and cinchonine when given as a combination were evaluated in Thai patients with falciparum malaria during acute infection and convalescence. The combination of quinine, quinidine and cinchonine was randomly given to thirteen patients at 400 mg or 600 mg (consisting of one-third of each component; 7 patients were enrolled in 400 mg regimen and 6 in 600 mg regimen) intravenously every 8 hours for 7 days. The drug combination was given again at day 35 to define the pharmacokinetics of each drug during convalescence. All patients with the 600 mg regimen had good response with 100% cure rate while patients with the 400 mg regimen had a good initial response but one patient recrudesed on day 46. This particular patient had plasma concentrations of all three drugs lower than the mean values of patients with sensitive responses. The plasma levels of quinine and quinidine obtained from the present study were higher than that expected from one-third of the conventional dose (600 mg) when given alone, suggesting drug combination interaction. The terminal half-lives of each of the three components were prolonged during acute malaria when compared to those obtained during convalescence.

Topics: Adult; Antimalarials; Cinchona Alkaloids; Drug Combinations; Humans; Malaria, Falciparum; Male; Quinidine; Quinine; Treatment Outcome

Red cell and plasma quinine-quinidine, and quinine concentrations in children with uncomplicated falciparum malaria who were treated with a combination of quinine/quinidine/cinchonine (combined drug) and quinine alone, respectively, were measured, using the extraction fluorescence method. The cure rates obtained with the high dose regimen of the combined drug (100%) were significantly higher than in the low dose regimen group (37.5%) (p less than 0.05), and the quinine regimen produced a 50% cure rate. Similar mild and transient ECG effects were noted in both the combined drug group and the quinine group. In patients treated with the combined drug, quinine-quinidine concentrations in both red cell and plasma of the high dose regimen group were significantly higher than those in the low dose regimen group (p less than 0.001, p less than 0.001). In quinine-treated patients, red cell quinine concentration in those with RII failure was significantly lower than that in patients with cure or RI failure (p less than 0.05). Both red cell and plasma levels of quinine-quinidine were higher than quinine levels. The red cell:plasma quinine-quinidine concentration ratios rose steadily to the high level from day 3 to day 6, while the ratio of quinine alone fluctuated around the low level and then gradually fell. The evidence suggests that red cell drug concentrations are more closely related to the outcome of treatment than to plasma concentrations and that the combined drug may be very useful for treatment of multi-drug-resistant P. falciparum infections. Further study is needed.

Topics: Antimalarials; Child; Child, Preschool; Cinchona Alkaloids; Dose-Response Relationship, Drug; Drug Combinations; Drug Evaluation; Erythrocytes; Female; Humans; Malaria, Falciparum; Male; Plasma; Quinidine; Quinine

Topics: Animals; Antimalarials; Chloroquine; Copper; Malaria, Falciparum; Malaria, Vivax; Mice; Oocysts; Parasitemia; Plasmodium; Plasmodium falciparum; Primaquine