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

TABLE 4.

Comparison of pharmacodynamic variables measured as calcineurin (CN) activity and their corresponding correlations after morning tacrolimus dose (0–12 h) and after night Tac dose (12–24 h) of twice-daily tacrolimus formulation.

Variables Morning dose (0–12 h) Night dose (12–24 h) p
Itrough (pmol RII/min·mg prot) 296.0 [277.1–316.3] 285.8 [266.1–307.0] 0.040 a
Inadir (pmol RII/min·mg prot) 220.1 [204.3–237.2] 238.7 [221.7–257.0] 0.002 a
Tnadir (h) 2.16 [1.25–3.49] 2.76 [1.47–4.26] 0.656 b
Itrough/Inadir 1.29 [1.25–1.34] 1.20 [1.15–1.24] 0.002 a
AUE Imin (pmol RII·h/min·mg prot) 127.7 [112.3–145.2] 120.1 [99.1–145.6] 0.572 a
AUE Inadir (pmol RII·h/min·mg prot) 262.4 [216.2–318.4] 245.9 [190.6–317.3] 0.449 a
Correlations c Morning dose (0–12 h) Night dose (12–24 h)
R p R P
I0 vs AUE0–12 h Imin −0.034 0.881
I12 vs AUE0–12 h Imin 0.115 0.609
I12 vs AUE12–24 h Imin −0.001 0.968
I24 vs AUE12–24 h Imin −0.255 0.252
I0 vs AUE0–12 h Inadir −0.134 0.552 - -
I12 vs AUE0–12 h Inadir 0.125 0.579 - -
I12 vs AUE12–24 h Inadir 0.158 0.491
I24 vs AUE12–24 h Inadir 0.252 0.257
I0 vs Inadir 0–12 h 0.899 <0.001
I12 vs Inadir 12–24 h 0.818 <0.001
a

Paired t-test.

b

Wilcoxon test.

c

Pearson’s correlation test.

Data is represented as geometric mean [95% CI] unless Tnadir that is expressed as median [interquartile range]. Itrough, trough CN activity at time 12 h for morning dose and at time 24 h for night dose; Inadir, maximum inhibition of CN activity; Tnadir, time to reach Inadir; AUE Imin, area under the effect-time curve of CN inhibition from each 12 h dose interval using Imin as baseline; Imin, minimum CN inhibition observed along 24 h interval; AUE Inadir, area under the effect-time curve of CN inhibition from each 12 h dose interval using the Inadir observed along 24 h interval as baseline; I0, morning pre-dose CN activity at time 0 h; C12, night pre-dose CN activity at time 12 h; C24, CN activity concentration at time 24 h; AUE0–12 h, area under the effect-time curve after the morning dose from 0 to 12 h; AUE12–24 h, area under the effect-time after the night dose from 12 to 24 h.