Comparison of capecitabine concentrations determined by microsampling versus plasma concentrations for therapeutic drug monitoring: a pilot study

Objectives: Therapeutic drug monitoring allows personalized dosing of chemotherapy, but is not well established for capecitabine. The aim of this study was to compare the concentrations of capecitabine and its metabolites obtained simultaneously by microsampling with plasma sampling and their acceptability to patients.Methods: Adults taking capecitabine for cancer had paired (duplicate) microsampling at steady state (hour 2 post dose) using Mitra (R) devices and venous blood samples for analysis. Capecitabine and metabolites were measured using a validated mass spectrometry assay. Correlation between the sampling methods was determined. Patients' preferences were elicited using a Likert numeric rating scale and pain by a Visual Analog Scale (range, 0-10).Key findings: Capecitabine concentrations from 10 patients (60 paired samples) by microsampling and plasma sampling were highly correlated (Pearson correlation: 0.97, Coefficients of determination: 0.94, P < 0.0001). Capecitabine concentrations in capillary sampling were consistently lower than the paired plasma concentration (median capecitabine capillary/plasma concentration ratio = 2851/3846 mu g/l 75%). The agreement between sampling matrices showed a 28% bias (95% Cl, 4.02-52.00). Participant ratings showed microsampling was the preferred method by all 10 patients. Most participants reported no pain with microsampling (median 0, range 0-1).Conclusion: Capecitabine concentration measured by microsampling and plasma sampling were highly correlated, but consistently lower in microsampling. Microsampling was the preferred method with minimal pain.