Evaluation of a novel micro-sampling device, Mitra™, in comparison to dried blood spots, for analysis of praziquantel in Schistosoma haematobium-infected children in rural Côte d'Ivoire.

Pharmacokinetic (PK) studies with paediatric populations are increasing in importance for drug development. However, conventional PK sampling methods are characterised by invasiveness and low patient adherence, unsuitable for use with sensitive population, such as children. Mitra™ is a novel volumetric absorptive micro-sampling device, which offers an alternative to the dried blood spotting (DBS) technique, a current popular sampling technique within PK studies. We tested Mitra™ for the first time in the framework of a randomised controlled trial in rural Côte d'Ivoire. Thirty-five school-aged children, infected with Schistosoma haematobium, were sampled with both DBS and Mitra™, at 10 time points after treatment with praziquantel (PZQ). An extraction method for PZQ from Mitra™ was developed, optimised and validated. Analytes, namely R- and S-praziquantel (R-/SPZQ) and the main human metabolite, R-trans-4-OH-praziquantel, were measured using liquid chromatography-tandem mass spectrometry and the results were compared with Bland-Altman analysis to determine agreement between matrices. PK parameters, such as maximal plasma concentration and area under the concentration-time curve, were estimated using non-compartmental analysis. While we observed strong positive correlation (R2 > 0.98) and agreement between both matrices within the calibration line and quality control samples, Mitra™ revealed higher concentrations of all the analytes in the majority of patients' samples compared to DBS sampling, namely 63% samples for RPZQ, 49% for SPZQ and 78% for the metabolite were overestimated. While T1/2 and Tmax were in agreement between both matrices, area under the curve and maximal blood concentration were up to 2× higher for Mitra™ samples, with P < 0.005 for all parameters except Cmax of SPZQ, which was not significantly different between the two matrices. The reasons for the higher PZQ concentrations, more pronounced in incurred Mitra™ samples compared to spiked samples, are yet to be fully explored. Mitra™ appears superior to DBS in terms of simplicity and practicality however labelling issues and the high price of Mitra™ are difficult to overlook.

RCT Entities:   Population Interventions Outcomes