Relationship between plasma and red blood cell concentrations of quinine in Brazilian children with uncomplicated Plasmodium falciparum malaria on oral therapy.

We determined the relationship between plasma and red blood cell concentrations of quinine in children with uncomplicated falciparum malaria from an endemic area of Amazonian region. Quinine was determined by high performance liquid chromatography with ultraviolet detection. In the steady state the ratio between plasma and red blood cell quinine concentration was 1.89 +/- 1.25 ranging from 1.05 to 2.34. This result demonstrated that quinine do not concentrate in red blood cell of Brazilian children and characterize the absence of interracial difference in this relationship.

Relationship between plasma and red blood cell concentrations of quinine in Brazilian children with uncomplicated Plasmodium falciparum malaria on oral therapy / Relação entre as concentrações plasmáticas e eritrocitárias de quinina em crianças com malária por Plasmodium falciparum não complicada em terapia via oral

We determined the relationship between plasma and red blood cell concentrations of quinine in children with uncomplicated falciparum malaria from an endemic area of Amazonian region. Quinine was determined by high performance liquid chromatography with ultraviolet detection. In the steady state the ratio between plasma and red blood cell quinine concentration was 1.89 ± 1.25 ranging from 1.05 to 2.34. This result demonstrated that quinine do not concentrate in red blood cell of Brazilian children and characterize the absence of interracial difference in this relationship.

Neste estudo foi determinada a relação entre as concentrações plasmáticas e eritrocitárias de quinina em crianças com malária falciparum não complicada, oriundas de área endêmica da Região Amazônica. A quinina foi detrminada por cromatografia líquida de alta eficiência. No estado de equilíbrio, a relação foi 1,89 ± 1,25 variando de 1,05 a 2,34. Estes resultados demonstraram que a quinina não se concentra nos eritrócitos das crianças e caracterizaram a ausência de diferença racial nesta relação.

Quinine levels in patients with uncomplicated falciparum malaria in the Amazon region of Brazil

We examined the plasmatic concentrations of quinine in patients with uncomplicated falciparum malaria in an endemic area of the Amazon region in Brazil in a prospective clinical trial, in which a standard three-day course of oral quinine plus doxycycline was used. We measured the quinine in the plasma samples on days 0 and 3by high performance liquid chromatography. The mean concentration of quinine was 6.04 ±2.21 µg/mL in male patients and 5.98 ±1.95 µg/mL in female patients. No significant differences in quinine concentration were observed between these two groups. All samples collected before starting treatment were negative for quinine. This information could help in the development of strategies for the rational use of antimalarial drugs in Brazil.

Quinine levels in patients with uncomplicated falciparum malaria in the Amazon region of Brazil.

We examined the plasmatic concentrations of quinine in patients with uncomplicated falciparum malaria in an endemic area of the Amazon region in Brazil in a prospective clinical trial, in which a standard three-day course of oral quinine plus doxycycline was used. We measured the quinine in the plasma samples on days 0 and 3 by high performance liquid chromatography. The mean concentration of quinine was 6.04 +/-2.21 microg/mL in male patients and 5.98 +/-1.95 microg/mL in female patients. No significant differences in quinine concentration were observed between these two groups. All samples collected before starting treatment were negative for quinine. This information could help in the development of strategies for the rational use of antimalarial drugs in Brazil.

Drug monitoring of quinine in men with nonsevere falciparum malaria: study in the Amazon region of Brazil.

Quinine sulfate has been the drug of choice for the treatment of the ever-increasing number of cases of falciparum malaria in tropical countries. Because of the spectrum of adverse effects produced by the drug in the so-called cinchona syndrome, the variation in its pharmacokinetics during the episodes of falciparum malaria, and the different therapeutic regimens proposed in different countries, the authors monitored quinine plasma concentrations in daily samples of 20 men of the Amazon region in Brazil with nonsevere falciparum malaria who were administered 1 g quinine sulfate every 12 hours for 7 days. Three blood samples were collected from each patient each day: two immediately before administration of the drug (7 am and 7 pm) and one at 11 am. A total of 440 samples were analyzed by a validated method developed in the authors' laboratories using the high-performance liquid chromatographic technique. The overall quinine plasma levels obtained varied from 1.52 to 16.89 microg/mL. From the second day of treatment, overall levels varied from 2.33 to 14.29 microg/mL; the peak concentrations showed values from 4.22 to 16.89 microg/mL, showing the efficacy of the therapeutic regimen used. Adverse effects (signs and symptoms of cinchonism) were observed in all patients. However, no cases of hypoglycemia were detected. Intrapatient comparisons of the obtained quinine plasma concentrations were statistically significant. The quinine dose may be reduced on day 4 of treatment when asexual parasitemia is absent. This way, no resistance to the drug is observed, cinchonism can be minimized, and good adherence to the regimen is obtained.

Pharmacokinetics of quinine in children.

Serum quinine concentrations were measured in seven children after intravenous infusion of quinine dihydrochloride, in eight children after intramuscular injection of quinine dihydrochloride, and in six children after nasogastric administration of a solution of quinine dihydrochloride. The mean (+/- SD) half-life of quinine was 11.1 +/- 4.8 hours, and the volume of distribution was 1.39 +/- 0.37 L/kg. To attain a serum level of 10 microgram/ml quinine, we suggest that children with severe malaria be given a loading dose of 20 mg/kg quinine dihydrochloride parenterally, followed by 7.5 mg/kg every 8 hours. Once recovery begins, quinine sulphate 10 mg/kg may be given orally every 8 hours. Serum concentrations should be monitored, if possible, because they vary greatly from person to person. Quinine is rapidly and completely absorbed after either intramuscular or nasogastric administration.