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Table 1.

Patients characteristics (n = 32).

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Fig 1.

Model performances-diagnostic plots.

Individual predicted versus observed concentrations of tacrolimus in whole blood (A) and in PBMC (B), population predicted versus observed concentrations of tacrolimus in whole blood (C) and in PBMC (D), weighted residuals versus individual predicted concentrations of tacrolimus in whole blood (E) and in PBMC (F).

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Fig 1 Expand

Table 2.

Tacrolimus pharmacokinetics parameters in whole blood and PBMC (n = 32).

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Table 2 Expand

Fig 2.

Relationship between area under the concentration–time curve from 0 to 12 h (AUC) of tacrolimus in whole blood (WB) and in peripheral mononuclear blood cells (PBMC).

The dotted line is the linear regression curve. (n = 32) (r2 = 0.51, p<0.001).

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Fig 2 Expand

Fig 3.

Influence of recipient ABCB1 1199G>A on whole blood and on intracellular (PBMC) areas under the tacrolimus (TAC) concentrations–time curve from 0 to 12 h (AUC).

Each symbol represents mean ± standard deviation of the mean. (n = 29 ABCB1 1199GG, n = 3 ABCB1 1199GA).

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Fig 3 Expand

Table 3.

Influence of single nucleotide polymorphisms on TAC pharmacokinetics in whole blood and in PBMC.

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Table 3 Expand

Table 4.

Pharmacodynamic parameters (n = 32).

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Table 4 Expand

Fig 4.

Tacrolimus (TAC) pharmacokinetic-pharmacodynamic relationship.

(A): Relationship between calcineurin maximum inhibition (CaNImax) and TAC maximum concentration (Cmax) in peripheral mononuclear cells (PBMC) or whole blood (WB). Black arrows show tacrolimus concentration inhibiting 37% (IC37) of calcineurin activity (65 pg/million of cells in PBMC and 11 ng/mL in whole blood) and greys arrows show tacrolimus concentration inhibiting 50% (IC50) of calcineurin activity (100 pg/million of cells in PBMC and 18 ng/mL in whole blood). (n = 32). Probability of intracellular target attainement (B). Targets are IC37 and IC50 in PBMC. IC: Inhibitory concentration.

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Fig 4 Expand