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Updated: Jan 20, 2026
Microsampling in Targeted Mass Spectrometry-Based Protein Analysis of Low-Abundance Proteins
Published on: January 13, 2023
Tacrolimus Area Under the Concentration Versus Time Curve Monitoring, Using Home-Based Volumetric Absorptive
Marte T Gustavsen1,2, Karsten Midtvedt1, Nils T Vethe3
1Department of Transplantation Medicine, Oslo University Hospital.
Background:
Therapeutic drug monitoring (TDM) of tacrolimus (Tac) is mandatory in renal transplant recipients (RTxR). Area under the concentration versus time curve (AUC) is the preferred measure for Tac exposure; however, for practical purposes, most centers use trough concentrations as a clinical surrogate. Limited sampling strategies in combination with population pharmacokinetic model-derived Bayesian estimators (popPK-BE) may accurately predict individual AUC. The use of self-collected capillary microsamples could simplify this strategy. This study aimed to investigate the potential of AUC-targeted Tac TDM using capillary microsamples in combination with popPK-BE.
Methods:
A single-center prospective pharmacokinetic study was conducted in standard-risk RTxR (n = 27) receiving Tac twice daily. Both venous and capillary microsamples (Mitra; Neoteryx, Torrance, CA) were obtained across 2 separate 12-hour Tac dosing intervals (n = 13 samples/AUC). Using popPK-BE, reference AUC (AUCref) was determined for each patient using all venous samples. Different limited sampling strategies were tested for AUC predictions: (1) the empiric sampling scheme; 0, 1, and 3 hours after dose and (2) 3 sampling times determined by the multiple model optimal sampling time function in Pmetrics. Agreement between the predicted AUCs and AUCref were evaluated using C-statistics. Accepted agreement was defined as a total deviation index ≤±15%.
Results:
The AUC from capillary microsamples revealed high accuracy and precision compared with venous AUCref, and 85% of the AUCs had an error within ±11.9%. Applying microsamples at 0, 1, and 3 hours after dose predicted venous AUCref with acceptable agreement. Patients performed self-sampling with acceptable accuracy.
Conclusions:
Capillary microsampling is patient-centered, making AUC-targeted TDM of Tac feasible without extended hospital stays. Samples obtained 0, 1, and 3 hours after dose, combined with popPK-BE, accurately predict venous Tac AUC.
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