Table 2. Population pharmacokinetics of F-araA in Aplastic anemia and Fanconi anemia.
| Parameter | BSA normalized | RSE (%) | Final model | RSE (%) | P-value | ||||
|---|---|---|---|---|---|---|---|---|---|
| CL (L/h/m2) | 4.84 | 9.8 | — | — | |||||
| WT, AAa | — | — | 7.12 | 10 | rs2295890: 3.8E−02; Diagnosis: 2.7E-07 | ||||
| WT, FA | — | — | 2.90 | 17 | |||||
| HET/MUT, AA | — | — | 5.03 | 15 | |||||
| HET/MUT, FA | — | — | 2.05 | 19 | |||||
| V (L/m2) | 27.56 | 6.4 | — | — | |||||
| Age on V | — | — | 21.25a exp (−0.013a age) | 11.8, 40.5 | 1.3E−02 | ||||
| k12 (h−1) | 0.35 | 7.3 | 0.36 | 7.6 | |||||
| k21 (h−1) | 0.19 | 6.5 | — | — | |||||
| Age on k21 | — | — | 0.14a exp (0.016a age) | 10.1, 26.5 | 1.6E−04 | ||||
| σ prop (CV%) | 0.19 | 3.6 | 0.19 | 3.6 | |||||
| −2 Log-likelihood | 312.34 | 2.4 | 262.51 | 2.1 | 3.9E−08 | ||||
| IIV, IDV | (CV%) | RSE (%) | (CV%) | RSE (%) | |||||
| CL | 0.69 | 0.21 | 10.3 | 12.0 | 0.51 | 0.22 | 11.0 | 11.8 | |
| V | 0.39 | 0.21 | 13.1 | 16.4 | 0.36 | 0.22 | 13.8 | 15.8 | |
| k12 | 0.37 | 0.18 | 17.5 | 36.5 | 0.41 | 0.19 | 15.4 | 35.7 | |
| k21 | 0.26 | 0.23 | 28.7 | 30.1 | 0.14 | 0.20 | 65.6 | 34.7 | |
Abbreviations: CL=clearance; F-araA=fludarabine; HET=heterozygous variant; IDV=inter-day variability; IIV=inter-individual variation; MUT=mutant; RSE=residual error; WT=wild-type genotype.
a
Covariate effect of rs2295890 and diagnosis on clearance. The covariates are defined as follows: rs2295890=(WT or HET/MUT); Diagnosis=(AA refers to Aplastic Anemia or FA-Fanconi Anemia).