Levels of primaquine and carboxyprimaquine in patients with malaria vivax from the Brazilian Amazon basin

Abstract

In the last two years, a substantial increase in the number of malaria vivax cases has occurred in the Brazilian Amazon basin. The adequate exposure of hypnozoites to primaquine is a matter of interest as these dormant forms are responsible for the maintenance or even the increase of malaria burden in endemic areas. The aim of this study was to estimate the levels of primaquine and carboxyprimaquine in whole blood samples of patients with P. vivax treated with chloroquine and an abbreviated regimen of primaquine (0.5 mg/kg/d for 7 days), with adequate clinical and parasitological outcomes after 180 days of follow-up. A total of 40 male patients met the criteria for inclusion in the study. Primaquine and carboxyprimaquine were measured by high-performance liquid chromatography. The levels of primaquine in whole blood samples ranged from 40-238 ng/mL, 42-196 ng/mL and 42-150 ng/mL on days 1, 3 and 7. The levels of carboxyprimaquine in whole blood samples ranged from 87-234 ng/mL, 96-252 ng/mL and 74-448 ng/mL on days 1, 3 and 7. These data provide a reliable estimation of exposure of the infecting parasite to primaquine. Based on the regional pattern of relapse, the estimated blood levels of primaquine can be considered effective against hypnozoites of the local circulating strains of P. vivax.

Transplacental Transfer of Primaquine and Neurobehavioral Development of Prenatally Exposed Rats

“…Most of the absorbed drug undertakes MAOmediated oxidative deamination to carboxy-PQ, an inactive metabolite, that is further metabolized through CYPs and phase-II enzymes [24][25][26]. A minor proportion of PQ is oxidized by CYPs (predominantly CYP2D6, a polymorphic enzyme) to form unstable hydroxyl metabolites (e.g., 5hydroxy-PQ) that are believed to account for drug parasiticidal activity [25][26][27]. Malarial patients with a CYP2D6 poor metabolizer phenotype are refractory to PQ treatment [25,26].…”

Enantioselective Interactions of Anti-Infective 8-Aminoquinoline Therapeutics with Human Monoamine Oxidases A and B

“…PQ is metabolized through both CYP P 450 and non-CYP mediated pathways [ 15 , 22 , 23 , 24 ]. Carboxyprimaquine (carboxy-PQ), generated through the monoamine oxidase (MAO)-dependent oxidative deamination pathway, is a major plasma metabolite of PQ [ 25 , 26 , 27 , 28 ]. Rapid metabolism of PQ, including by MAO pathways, results in a short half-life of this drug, and has generally required a long (14 day) treatment regimen for malaria radical cure [ 29 , 30 , 31 ].…”

Development of Electro-Analytical Methods Using Sensors Modified With Nanomaterials for Determination of Primaquine, Inhhq, Thiomersal and Creatinine

“…Primaquine is metabolized forming several species but the major ones are carboxyprimaquine and glucuronide conjugates [74]. Primaquine, in its original form, was detected, at the μg L −1 level, in blood of patients submitted to multiple oral dose treatment [75]. In urine, a small percent of the drug is still in the original form at the ng L −1 level [76].…”