Tacrolimus Measured in Capillary Volumetric Microsamples in Pediatric Patients-A Cross-Validation Study.

Abstract

Background:Therapeutic drug monitoring of tacrolimus (Tac) is mandatory in solid organ transplant (SOT) recipients. Finger-prick microsampling is more flexible and tolerable during the therapeutic drug monitoring of tacrolimus and has been shown to be applicable in adult SOT recipients. In this study, a previously validated method applying volumetric absorptive microsampling (VAMS) to measure Tac in adults was cross-validated in a pediatric population.Methods:Patients with SOT scheduled for standard posttransplant follow-up visits were recruited. Blood samples were obtained by trained phlebotomists using standard venipuncture and capillary microsampling, before the morning dose of Tac as well as 2 and 5 hours after dosing. Tac concentrations were quantified using liquid chromatography–tandem mass spectrometry. Concordance between Tac concentrations obtained with venipuncture and VAMS was evaluated using Passing–Bablok regression, calculation of absolute and relative differences, and percentage of samples within ±20% and ±30% difference.Results:A total of 39 SOT patients aged 4–18 years (22 male) were included. The median (range) predose venous blood concentration was 4.8 (2.6–13.6) mcg/L, with a difference between VAMS and venous blood samples of −0.2 ± 0.7 mcg/L. The relative mean difference was −1.3% [95% confidence interval (CI), −5.9% to 3.4%]. Ninety-two percent and 97% of the sample pairs demonstrated differences within ±20% and ±30%, respectively. Postdose (2 hours and/or 5 hours, n = 17) median concentration in venous blood was 7.9 (4.8–19.2) mcg/L. The difference between VAMS and venous blood samples was 0.1 ± 1.0 mcg/L, with a relative mean difference of −2.5% (95% confidence interval, −8.8% to 3.8%). Eighty-eight percent of the postdose sample pairs were within ±20% difference, and all were within ±30% difference.Conclusions:Tac concentrations can be accurately measured using VAMS technology in pediatric SOT recipients. This makes home-based Tac monitoring feasible in the pediatric population.