Abstract
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 (LSS) 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 utilizing 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 two separate 12-h Tac dosing intervals (n=13 samples/AUC). Utilizing popPK-BE, reference AUC (AUCref) was determined for each patient using all venous samples. Different LSS were tested for AUC predictions: 1) the empiric sampling scheme; 0, 1, and 3 h post-dose and 2) three 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%.The AUC from capillary microsamples revealed high accuracy and precision compared to venous AUCref, and 85% of the AUCs had an error within ±11.9%. Applying microsamples at 0, 1, and 3 h post-dose predicted venous AUCref with acceptable agreement. Patients performed self-sampling with acceptable accuracy.Capillary microsampling is patient-centered, making AUC-targeted TDM of Tac feasible without extended hospital stays. Samples obtained 0, 1, and 3 h post-dose, combined with popPK-BE accurately predict venous Tac AUC.
Citation
ID:
40436
Ref Key:
gustavsen2019tacrolimustherapeutic