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. 2011 Feb;71(2):207–223. doi: 10.1111/j.1365-2125.2010.03815.x

Table 6.

Predictive performance of population models for prediction of tacrolimus exposure in adult kidney transplant recipients

Model Limited sampling equations Times used (h) r2 MPE(µg h l−1) MPPE(%) RMSE(µg h l−1) MAPE(%) % AUCp within 15% AUCf Reference
1a CL/F = 23.6 + 31.9/POD + 76.7/AST l h−1 0 0.34 −5.9 −4.9 22.3 26.4 30 [59]
1b V/F = 1070 l 0, 1 0.65 2.9 5.0 27.0 22.9 30
1c ka = 4.48 h−1 (fixed) 0, 1, 2 0.71 5.2 5.0 14.6 19.2 45
1d IIV CL/F = 42% 0, 1, 2, 4 0.75 1.9 1.3 12.5 12.5 55
1e* IIV V/F = 111% 0, 1, 2, 4, 6 0.83 3.2 2.3 9.2 8.6 70
1f* RREa = 3.7 ng ml−1 0, 1, 4 0.74 0.1 0 12.9 13.0 60
1g 0, 4 0.68 −7.4 −5.2 16.2 15.9 45
2a CL = 1.81 × [1 + POD2.54 / (POD2.54 + 3.812.54)] × PRED l h−1 0 0.27 8.2 9.3 20.1 17.5 40 [60]
2b PRED = 1 + 0.575 (If prednisolone dose >25 mg or 1 if not) 0, 1 0.75 0.7 1.2 30.0 21.8 25
2c V = 98.4 l 0, 1, 2 0.83 3.9 4.7 13.7 15.4 50
2d† F = 13.7% 0, 1, 2, 4 0.93 1.6 1.6 6.6 7.4 75
2e* ka = 4.5 h−1 (fixed) 0, 1, 2, 4, 6 0.95 −2.1 −1.4 4.9 4.6 90
2f* IIV CL = 31% 0, 1, 4 0.91 −0.1 −0.1 8.1 9.2 70
2g* IIV V = 79% 0, 4 0.88 −3.3 −4.1 9.9 9.7 75
IIV F = 32%
RREa = 0.96 ng ml−1
RREp = 18.6%
3a CL (CYP3A5*3/*3) = 3.7 l h−1 0 0.52 30.7 25.7 43.0 31.6 20 [61]
3b CL (CYP3A5*1/*3) = 5.5 l h−1 0, 1 0.64 11.0 14.4 21.1 20.8 40
3c Vc = 42 l 0, 1, 2 0.73 8.2 10.0 18.3 16.4 50
3d Vp = 42 l 0, 1, 2, 4 0.86 6.4 6.5 14.9 12.7 55
3e* Q = 10 l h−1 0, 1, 2, 4, 6 0.89 4.7 6.7 12.1 9.7 60
3f* F = 23% (fixed) 0, 1, 4 0.82 6.7 9.2 17.7 13.6 55
3g F = 19.5% (If prednisone dose >10 mg) 0, 4 0.72 18.3 14.8 28.3 23.8 40
ka = 1.6 h−1
IIV CL = 19%
IIV Vc = 28%
RREp = 23%
4a CL/F = 22 + 34 (if CYP3A5*1/*1 or *1/*3) + 10 (if MDR-1 0 0.54 20.9 24.2 31.9 28.1 35 [62]
4b 1236CC, 2677GG or 3435CC) l h−1 0, 1 0.69 −1.2 −0.5 29.1 25.1 40
4c Vc/F = 142 l 0, 1, 2 0.82 −2.4 −2.4 14.2 14.1 50
4d* Vp/F = 192 l 0, 1, 2, 4 0.93 −8.6 −7.2 9.4 9.4 65
4e* Q/F = 43 l h−1 0, 1, 2, 4, 6 0.94 −4.7 −5.0 5.4 6.5 65
4f* ka = 2.18 h−1 0, 1, 4 0.83 −4.6 −4.6 13.0 14.1 55
4g IIV CL/F = 46% 0, 4 0.82 9.8 8.0 14.8 15.8 50
IIV Vc = 33%
IIV Vp = 31%
RREa = 0.02 ng ml−1
RREp = 29%
5a CL/F = 863/HAEM 0 0.42 18.9 17.0 29.4 22.5 30 [63]
5b Vc/F = 147 l 0, 1 0.70 −6.3 −6.7 15.8 13.8 50
5c Vp/F = 500 l (fixed) 0, 1, 2 0.76 −2.4 −2.7 13.5 13.5 50
5d* Q/F = 60 l h−1 0, 1, 2, 4 0.87 −1.1 −1.3 9.5 9.8 80
5e* ka = 6.5 h−1 0, 1, 2, 4, 6 0.91 −0.2 −0.2 8.1 7.7 80
5f* IIV CL/F = 30% 0, 1, 4 0.86 −0.7 −0.3 10.1 8.1 65
5g IIV Vc/F = 26% 0, 4 0.69 20.1 17.3 26.1 22.9 25
IIV Q/F = 63%
IIV ka = 15%
RREa = 1.5 ng ml−1
RREp = 10%
ISBA Population model not published 0.25, 1, 3 0.92 5.3 6.6 8.0 9.6 85 [54]
Web-based Information on covariates (postoperative day,
service* diabetes status, assay used) is supplied by the user

AST, aspartate transaminase; CV, coefficient of variation; CL, clearance, CL/F, apparent clearance; CYP3A5, cytochrome P450 3A5; F, bioavailability; ka, absorption rate constant; HAEM, haematocrit; IIV, interindividual variability; IOV, interoccasional variability; MAPE, median absolute percentage prediction error; MDR-1, multiple drug resistant protein 1; MPE, median prediction error; MPPE, median percentage prediction error; POD, postoperative day; Q, intracompartmental clearance; Q/F, apparent intracompartmental clearance; RMSE, root median squared prediction error; RREa, additive residual random error; RREp, proportional residual random error; V, volume of distribution; Vc, volume of distribution of central compartment; Vp, volume of distribution of peripheral compartment; V/F, apparent volume of distribution; IIV + IOV.

*

Acceptable bias and imprecision.

†

Best performance of all equations with regard to practicality and performance.