Background: Significant variations in tacrolimus (TAC) pharmacokinetics (PK) occur across whole blood, plasma, and peripheral blood mononuclear cells (PBMCs). In the present study, TAC plasma levels were estimated based on TAC whole blood levels, and the influence of genetic polymorphisms on the PKs of TAC were compared between whole blood, plasma, and PBMCs. Methods: Whole blood, plasma, and PBMC samples of 36 kidney allograft recipients were collected at 0–12 hours after the morning dose after 1 month of therapy. TAC levels in whole blood (C wb ), plasma (C p ), and PBMCs were determined using liquid chromatography–tandem mass spectrometry. TAC C p was estimated based on C wb and hematocrit. PK parameters of TAC in whole blood, plasma, and PBMC were estimated. The influence of CYP3A5 and ABCB1 genotypes on TAC exposure was evaluated. Results: TAC whole blood trough concentration (C 0 ), maximum concentration (C max ), and area under the concentration–time curve (AUC 0–12 ) were 8.60 ± 5.59 ng/mL, 20.1 ± 7.69 ng/mL, and 144 ± 69.4 ng⋅h/mL, respectively; 0.21 ± 0.12 ng/mL, 0.51 ± 0.35 ng/mL, and 3.02 ± 1.68 ng⋅h/mL, respectively, in plasma; and 0.026 ± 0.017 ng/10 6 PBMCs, 0.078 ± 0.047 ng/10 6 PBMCs, 0.49 ± 0.30 ng⋅h/10 6 PBMCs, respectively. A moderate correlation was observed between C 0 , C max , and AUC 0–12 in plasma and PBMCs ( P T) significantly influenced TAC exposure in both plasma and PBMC.
Lu et al. (Fri,) studied this question.