F-araA PopPK and PG:
F-araA PK was available for 169 patients enrolled in the study.
Thirty-two (11.7%) and 19 (10.3%) patients carried variant allele forNT5E and DCK polymorphisms. The population pharmacokinetic
parameters are shown in Table 2 . The median post hoc estimated
F-araA AUC and CL for the first dose was 19 (3-81) μmol*h/mL and 7
(2-38) L/h/m2. The PopPK model estimated significant
inter-individual variation (IIV) in F-araA PK (27 and 19 fold in AUC and
CL). F-araA Cl was significantly lower in patients with NT5Evariant rs2295890 genotype (5.37 vs 7.17 L/h/m2;
p=0.001). These differences translated to significantly higher AUC in
patients with variant rs2295890 genotype (26.5 vs 18.0 µM*h; p=0.01)
(Figure 1). The NT5E variant explained 4.5% of the IIV on the
clearance of F-araA. None of the other demographic/biochemical
covariates including DCK polymorphism explained IIV in F-araA PK.