Dried Blood Spot Sampling for Tacrolimus and Mycophenolic Acid in Children: Analytical and Clinical Validation

Abstract

A DBS assay was developed for tacrolimus and MPA. Tacrolimus venous concentrations could be adequately predicted from DBS. DBS analysis of MPA seemed to be a semiquantitative measurement at the most when compared with conventional plasma analysis, considering the high variability between observed and predicted concentrations. Next, home-based DBS sampling of tacrolimus for the purpose of therapeutic drug monitoring will be implemented into routine clinical care.

Therapeutic drug monitoring of tacrolimus and mycophenolic acid in outpatient renal transplant recipients using a volumetric dried blood spot sampling device

“…For mycophenolic acid, the observed geometric mean DBS to plasma concentration ratio of 0.66 was in line with those described by Martial et al . and Arpini et al . , who reported ratios of 0.77 ( n = 38) and 0.61 ( n = 77), respectively.…”

“…With regard to the DBS to WB or plasma conversion factors, a few similar studies could be identified. For tacrolimus, the observed geometric mean DBS to WB concentration ratio of 0.93 was not in line with the conversion factor of 1.31 ( n = 40) reported by Martial et al ., who found higher tacrolimus concentrations in DBS than in WB . Various other studies ( n = 18–172) in adult and paediatric solid organ transplantation have been performed on the subject, and reported a range of geometric mean differences of −0.70 to +0.29 μg l −1 between tacrolimus DBS and WB concentrations .…”

“…Correction of DBS concentrations is performed based on the patientspecific or average haematocrit, often in combination with the red blood cell to plasma partition ratio [25,26]. Translation strategies without haematocrit correction are performed based on the average DBS to WB or plasma ratio [21,44,45] or the DBS to WB or plasma concentration regression fit slope or equation [44,[46][47][48][49]. To investigate the need for and extent of correction of tacrolimus and mycophenolic acid DBS concentrations in the present study, a clinical pilot study was conducted from February to June 2016.…”

“…Over the past decade, various methods for immunosuppressant determination in DBS samples have been described, with the most recent advances including multi‐analyte assays for simultaneous quantification of up to five immunosuppressants from one blood spot . Unfortunately, only a few of these multi‐analyte assays have been clinically validated . Additionally, interpretation of these studies often proves cumbersome because of a limited sample size, unsatisfactory statistical work or the absence of clinical acceptance limits.…”

“…It thereby creates options for more frequent monitoring based on optimal sampling time points [12], at an overall reduced patient burden and higher cost efficiency [13] as compared with conventional TDM. Over the past decade, various methods for immunosuppressant determination in DBS samples have been described, with the most recent advances including multi-analyte assays for simultaneous quantification of up to five immunosuppressants from one blood spot [14][15][16][17][18][19][20][21]. Unfortunately, only a few of these multi-analyte assays have been clinically validated [17,[20][21][22][23][24].…”