腎移植レシピエントにおけるタクロリムストラフ血中濃度とAUCの関係性に与えるプロトンポンプ阻害薬の影響

抄録

A single-trough blood concentration (C0) point is considered useful in the therapeutic drug monitoring of tacrolimus (Tac). However, whether or not the relationship between C0 and area under the concentration time curve (AUC) changes when a proton pump inhibitor (PPI), which is potentially interacted with Tac, is concomitantly used remains unclear.

This retrospective study included renal transplant recipients who were taking Graceptor^® for immunosuppression, admitted to this hospital between January 2016 and March 2021, and evaluated for AUC0–12 of Tac. The relationship between C0 and the AUC was plotted and examined with and without concomitant PPI (rabeprazole or lansoprazole) use.

The relationship between C0 and AUC0–12 in 79 subjects is expressed as y = 21.0x + 37.3, R² = 0.805 in the group with PPI and y = 21.9x + 24.5, R² = 0.881 in the group without PPI, yielding a correlation coefficient difference of T = 1.12 (P = 0.263). However, in subpopulations with a low dose-adjusted trough concentration (C0/D) ratio defined as C0/D lower than 50 [(ng/mL)/(mg/kg/d)] and the intermediate (C0/D 50 – 100) group, the correlation coefficients between C0 and AUC with concomitant PPI were R² = 0.742 and R² = 0.586, respectively.

In conclusion, rabeprazole or lansoprazole has no clinically significant effect on the relationship between C0 and AUC of Tac in renal transplant recipients. However, in cases with Tac C0/D less than 100, the AUC evaluation by multiple blood sampling is recommended in that PPI use may affect the good correlation with C0 and AUC.