Influence of age and genetic polymorphisms on pharmacokinetic parameters. (A) Correlation between age and the average AUC_0-48h (upper panel) and between age and the average MTX clearance (lower panel) of each patient. (B) Association of the SLCO1B1 rs4149056 SNP with pharmacokinetic parameters. Genotype-dependent change in the area under the concentration time curve (AUC)_0-48h, the peak MTX plasma concentration at the end of infusion (C_24h), and the MTX clearance. Error bars show 5% to 95% percentiles. Shown are P values obtained from the multiple regression models with age, sex, MRD class, WBC, and genotypes as independent variables. Jonckheere trend test assuming an a priori ordering consistent with an additive allelic effect: P < .0001 (AUC_0-48h and C_24h), P < .001 (clearance).