Comparison of plasma, venous and capillary blood levels of piperaquine in patients with uncomplicated falciparum malaria

Abstract

PurposeDihydroartemisinin-piperaquine (DP) is a fixed-dose artemisinin-based combination treatment. Field pharmacokinetic studies would be simplified and facilitated by being able to use small volume capillary assays rather than venous blood. The aim of this study was to describe the relationship between piperaquine concentrations measured in capillary blood, venous blood and venous plasma.MethodsSamples of plasma, whole blood obtained by venesection and capillary blood were taken simultaneously from patients with uncomplicated Plasmodium falciparum malaria treated with DP between 0 and 9 weeks after treatment. Piperaquine concentrations in venous and capillary samples were measured using solid phase extraction and analysis by liquid chromatography with ultraviolet detection.ResultsA total of 161 sets of the three measures were obtained from 54 patients. Piperaquine concentrations in the venous blood samples were approximately twofold higher and those in the capillary blood samples were threefold higher than the corresponding venous plasma concentrations. Capillary blood piperaquine concentrations were approximately 1.7-fold higher than venous blood concentrations, and this difference also increased with time.ConclusionDifferences in whole blood and plasma levels of piperaquine suggest compartmentalisation of the drug within blood cells, as also occurs with the structurally related quinoline chloroquine. The relationship between piperaquine concentrations in the venous plasma, venous blood and capillary blood is variable and unpredictable at low concentrations. However, within the range of concentrations usually present in patients between 3 and 21 days after treatment with currently recommended doses, the relationship between capillary and venous whole blood is predictable; consequently, capillary blood sampling can be used in field assessments.

Evidence of Plasmodium falciparum Malaria Multidrug Resistance to Artemisinin and Piperaquine in Western Cambodia: Dihydroartemisinin-Piperaquine Open-Label Multicenter Clinical Assessment

“…A plasma PP concentration of Ն30 ng/ml at day 7 was considered evidence of adequate PP exposure (27). The relationship between the concentration of PP in capillary blood spotted onto filter paper (cb) and that in plasma (pl) was calculated using the following correlation: log(e) PPpl ϭ [log(e) (PPcb ϫ 0.974)] Ϫ 1.072 (30).…”

Why Dried Blood Spots Are an Ideal Tool for CYP1A2 Phenotyping

“…Differences between capillary and venous concentrations have been found for several other small molecules (e.g. piperaquine, paracetamol) [7,8]. However, lower capillary concentrations of caffeine and paraxanthine compared to venous concentrations, have, to the best of our knowledge, not been described before.…”

“…First of all, being a capillary sampling technique, the correlation between venous and capillary concentrations is one of the key points that needs to be evaluated when setting up DBS-based methods [7,8]. Furthermore, adequate interpretation of DBS results requires comparison with plasma or serum concentrations, as clinical reference intervals are commonly based on the latter [9].…”

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

“…Being a microsampling technique, in which small volumes of blood are collected and processed, analytical instruments involved in DBS analysis should provide sufficient sensitivity. Furthermore, when capillary DBS are analyzed, knowledge of the correlation between capillary and venous concentrations of the analyte of interest is needed [32,33].…”