Therapeutic Drug Monitoring of Methotrexate on the Pediatric Oncology Ward: Can Blood Sampling From Central Venous Accesses Substitute for Capillary Finger Punctures?

Abstract

Intravenous methotrexate therapy with subsequent calcium folinate rescue is widely used for treatment of various neoplastic diseases, both in adults and in children. The optimization of the methotrexate dose and/or the calcium folinate rescue is based on pharmacokinetic data calculated from plasma concentrations collected after cessation of the methotrexate infusion. The aim of the present study was to evaluate the possibility of substituting capillary blood samples with blood samples drawn from central venous catheters (PORT-A-CATH) for therapeutic drug monitoring of methotrexate on the pediatric oncology ward. Nine cancer patients (4 females and 5 males; median age: 15 years; range: 5-20 years) were included. The quantitative analysis of methotrexate was carried out by fluorescence polarization immunoassay (FPIA). The concentrations of methotrexate in venous and capillary samples were closely correlated (rs = 0.98; P < 0.0001; n = 71). The venous/capillary plasma concentration ratio was 1.00 [median value; interquartile range (IQR): 0.882-1.094]; for 85% of the data points the ratio was 0.8 to 1.2, independent of drug concentration. The observed plasma concentration differences in blood samples drawn from central venous accesses and obtained from capillary blood samples in this study could have altered the calcium folinate rescue at 1 treatment occasion only. Plotting all measured methotrexate concentration time data for the individual patients during the elimination phase, on a chart including a normal elimination curve, is mandatory to enable proper handling of the subsequent rescue after high-dose methotrexate therapy. Blood sampling from the central venous access can be used only under certain circumstances for therapeutic drug monitoring of methotrexate. Carefully evaluated standardized instructions regarding rinsing, flushing, and discarding waste volumes, as well as precautions to minimize the required blood volume, are needed.