. 2021 Mar 17;12:636048. doi: 10.3389/fphar.2021.636048

TABLE 2.

Comparison of tacrolimus (Tac) pharmacokinetic variables in whole blood and their corresponding correlations after morning Tac dose (0–12 h) and after night Tac dose (12–24 h) of twice-daily Tac formulation.

Variables	Morning dose (0–12 h)	Night dose (12–24 h)	p
C_trough (ng/ml)	6.72 [6.00–7.52]	6.03 [5.34–6.82]	0.047 ^a
C_max (ng/ml)	18.20 [15.58–21.25]	11.12 [9.37–13.20]	<0.001 ^a
T_max (h)	1.52 [1.14–1.98]	1.87 [1.03–2.81]	0.182 ^b
AUC (ng·h/ml)	115.4 [104.2–127.9]	92.4 [81.5–104.8]	<0.001 ^a
C_trough/AUC	0.058 [0.054–0.062]	0.065 [0.061–0.070]	0.014 ^a
PTF (%)	112.3 [92.3–136.6]	40.6 [22.4–73.4]	0.006 ^a
SFI (%)	161.6 [123.8–211.1]	46.5 [24.4–88.7]	0.003 ^a
C_average (ng/ml)	9.62 [8.68–10.66]	7.70 [6.79–8.73]	<0.001 ^a
CL/F (mg·L/ng·h)	15.74 [12.44–19.91]	19.66 [15.13–25.54]	<0.001 ^a
Correlations ^c	Morning dose (0–12 h)		Night dose (12–24 h)
	R	P	R	p
C₀ vs AUC_0–12 h	0.696	<0.001	—	—
C₁₂ vs AUC_0–12 h	0.810	<0.001	—	—
C₁₂ vs AUC_12–24 h	—	—	0.748	<0.001
C₂₄ vs AUC_12–24 h	—	—	0.856	<0.001
C₀ vs C_{max 0–12 h}	0.341	0.120	—	—
C₁₂ vs C_{max 12–24 h}	—	—	0.711	<0.001

^{^a}

Paired t-test.

^{^b}

Wilcoxon-test.

^{^c}

Pearson’s correlation test.

Data is represented as geometric mean [95% CI] unless T_max, that is expressed as median [interquartile range]. C_trough, trough concentration corresponding at time 12 h for morning dose and at time 24 h for night dose; C_max, maximum peak Tac concentration; T_max, time to reach C_max; AUC, area under the concentration-time curve from each 12 h dose interval; PTF, peak-trough fluctuation index defined as [(C_max − C_trough)/C_average]; SFI, swing fluctuation index defined as [(C_max − C_trough)/C_trough]; C_average, average Tac concentration from each 12 h dose interval; CL/F, clearance/bioavailability ratio; C₀, morning pre-dose concentration at time 0 h; C₁₂, night pre-dose concentration at time 12 h; C₂₄, Tac concentration at time 24 h; AUC_0–12 h, area under the concentration-time curve after the morning dose from 0 to 12 h; AUC_12–24 h, area under the concentration-time curve after the night dose from 12 to 24 h.