Table 1.
Summary of published population pharmacokinetic models for tacrolimus in paediatric liver transplant recipients
| Reference | n | Median/mean age and range (years) | Time post-transplantation | Pharmacokinetic parameters | BSV CL (%) | BSV V (%) |
|---|---|---|---|---|---|---|
| Garcia Sanchez et al. [15]* | 18 | 9.1¶ 0.3–16.0 | 2.9 months¶ 1 day to 6.8 years | CL = 10.4 × (WT/70)0.75 × e(−0.00032T) × e(−0.057BILI) × (1 − 0.079 × ALT) (l h−1) F = 20% (fixed) | 24.3 | NR |
| Sam et al. [14]* | 20 | 3.7** 1.1–13.9 | 0–7 days | CL = 1.46 × (1 + 0.339 × (AGE − 2.25) (l h−1) V = 39.1 × [1 + 4.57 × (BSA − 0.49)] (l) BILI <200 μmol l−1: F = 0.197 × (1 + 0.0887 × WT − 11.4) (%) BILI ≥200 μmol l−1: F = 0.197 × (1 + 0.0887 × WT − 11.4) × 1.61 (%) | 33.5 | 33.0 |
| Yasuhara et al. [30]* | 33§ | 4.2** 0.3–15.0 | 52 days** | CL = (0.0749 + 0.000457 × POD) × [15 × (WT/15)0.290] (l h−1) V = 2.76 × [15 × (WT/15)0.290] (l) F = 19% | 52.1 | 27.4 |
| Staatz et al. [13]† | 35 | 5.7** 0.5–16.6 | NR | CL/Fwhole liver = 44 (l h−1) CL/Fcut-down liver = 5.75 (l h−1) V/F = 617 (l) | 110–297¶¶ | |
| Guy-Viterbo et al. [19]* | 42 | 1.4¶ 0.5–10.9 | From the day after transplantation until the patient experienced a rejection episode or, alternatively, until the end of the first year | CL/F = 0.001 × [1 + (314 × TIME)/(17.4 + TIME)] × [(Size/WT)/median(Size/WT)]0.12 × [Hct/29]−0.85 (l day−1)†† V1/F = 253 × (WT/10.2)0.9 (l) V2/F = 100 fixed Q/F = 115 (l day−1) | 54.8 | 77.5 |
| Abdel Jalil et al. [18]* | 43 | 5.0** 0.7–17.6 | First year post-transplantation | CL/F = 12.9 × (WT/13.2)0.75 × e(−0.00158 × POD) × e(0.428 × hFLAG)‡‡ (l h−1) | 40 | NR |
| Wallin et al. [17]‡ | 73 | 3.5¶ 0.4–16.9 | First year post-transplantation | CL/F = 0.148 + (1.37 × POD3.78)/(5.383.78 + POD3.78) (l h−1 kg−0.75) V/F = 27.2 (l kg−1) | NR | 90 |
| Fukudo et al. [12]* | 100 | 1.2¶ 0.1–15.0 | First 50 days post-transplantation | CL/F = (0.134 × 1.8iFLAG + 0.0181 × 2hFLAG × XPOD) × 8.6 × (WT/8.6)0.341 × e(−0.0358 × AST/53) (l h−1 kg−1)§§ V/F = 17.1 × 8.6 × (WT/8.6)0.341 (l) | 48.7 | 82.6 |
Abbreviations are as follows: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BILI, bilirubin concentration; BSA, body surface area; BSV, between-subject variability; CL, clearance; CL/F, apparent oral clearance; F, bioavailability; Hct, haematocrit; HF, hepatic function; n, number of patients; NR, not reported; POD, postoperative day; Q/F, intercompartmental clearance; T, time after initiation of treatment; TIME, time after transplantation; V, volume of distribution; V/F, apparent volume of distribution; V1/F, apparent central volume of distribution; V2/F, apparent peripheral volume of distribution; and WT, bodyweight.
Tacrolimus whole blood concentrations were measured using the microparticle enzyme immunoassay by use of an IMx analyser.
Tacrolimus whole blood concentrations were measured using a validated high-performance liquid chromatography tandem mass–spectrometry assay specific for the parent drug.
Tacrolimus whole blood concentrations were measured using either the EMIT 2000 assay (Siemens Healthcare) or a validated high-performance liquid chromatography tandem mass–spectrometry assay specific for the parent drug.
A total of 55 patients were included in this study, among whom 33 contributed to the development of the population pharmacokinetic model. The data regarding age and time post-transplantation pertain to the entire cohort.
Median value.
Mean value.
Equation not completely provided by authors.
If the patient was a CYP3A5*1 allele carrier, then hFLAG = 1; otherwise, 0.
If POD was <21, then XPOD = POD; otherwise, XPOD = 21; if the donor was a CYP3A5*1 allele carrier, then hFLAG = 1; otherwise, 0; and if the intestinal MDR1 mRNA level was >0.22 amol (μg total RNA)−1, then iFLAG = 1; otherwise, 0.
As reported by Staatz et al. in their article [13].