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

Abstract

SUMMARYWe 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. KEYWORDS:Quinine; Quinine levels; Malaria, Chromatography.In the last decade there has been an effort at monitoring the blood levels of antimalarials in patients with falciparum malaria, an important tool in the evaluation of efficacy and effectiveness of antimalarial drugs 4,5 . The response of the developing malaria parasite to antimalarials is largely determined by the concentration of drug accessible to the parasite within the red cell and its sensitivity to that drug 4 . The level of antimalarial drug in the plasma is proportional to the concentration within the parasitized red cell and it is determined by several independent variables as the drug formulation, age, race, immunity, the fraction of drug absorbed, the apparent volume of distribution and the clearance 5,6,7 .There is a lack of knowledge about the relationship between plasma and red blood cell concentrations of quinine in Brazilian children with uncomplicated falciparum malaria in which the standard treatment with oral quinine was used 1 . This is essential for the success of the treatment once a marked interpersonal and interracial difference in quinine disposition have been demonstrated 3,4,5 . Therefore, this work was done to elucidate this relationship in an endemic area of Amazon region, in a prospective clinical treatment trial.This study was conducted from January 2006 to January 2007, with 10 male children with signs and symptoms of uncomplicated P. falciparum malaria. Their characteristics were as follows (means ± SDs): age, 9.2 ± 3.1 years (age range; five to 13 years); body weight, 21.2 ± 4.1 Kg, erythrocyte count, 3.21 ± 0.52 x 10 6 /µL; white blood count, 11,300 ± 4700/µL. The median initial parasitemia was 2100/µL (range; 900 to 4500/µL). The patients were admitted to the public Hospital of Cachoeira do Piriá, Brazil. Informed consent was obtained from their parents. Children with severe or mixed malaria were excluded. Patients who had taken any antimalarial drugs within the previous 48 hours were also excluded. This study was approved by the ethics committee of the Tropical Medicine Center of Para Federal University.After clinical assessment and confirmation by microscopic examination of blood smears, all patients were treated with 3-day oral treatment regimen of quinine base (487.5 mg), followed by doxycycline hydrochloride for five days and primaquine phosphate in the last day. Reappearance of infection was assessed for at least 28 days, by clinical eval...

The antimalarial drug quinine interferes with serotonin biosynthesis and action

“…depending on the transporters expressed by cells), and between in vivo physiological environments, as affected by interactions between cells, neurotransmitters and hormones as well as organ type. For example, the level of QN within the brains of patients is thought to be lower than in peripheral tissues due to the blood-brain barrier32. Such considerations may mitigate the fact that the effective QN concentrations used in certain of our in vitro experiments with the RN46A cells were higher than the recommended therapeutic dose, approaching QN concentrations that are toxic to mammalian cells.…”