Population Pharmacokinetics Of High-dose Methotrexate In Children With Acute Lymphoblastic Leukemia

[Objective] To evaluate the population pharmacokinetics of high-dosemethotrexate(HDMTX) in children with acute lymphoblastic leukemia (ALL).[Methods] Intravenous solution with HDMTX(3g·m^-2) was given to 96 childrenwith ALL, 376 MTX plasma concentrations were measured mainly between 24to 68h after beginning the infusion and fluorescence polarizationimmunoassay (FPIA) was used to determine MTX plasmaconcentrations. Population pharmacokinetics model and parameters wereestimated by NONMEM software. The fixed effect factors, such asage,gender,height, body weight, body surface area, race, hydration andalkalization on pharmacokinetic parameters were evaluated and thenobtained the final regression modle.[Results]The following population parameters were obtained using atwo-compartment model: CL₁(clearance of central compartment)=5.04×(1-0.356×GEND)×BSA^0.777+(OH1/100)^0.514(L·h^-1), V₁(volume of centralcompartment)=16.1 (L), CL₂(clearance of peripheral compartment)=0.203×(AGE/10)^1.56(L·h^-1), V₂(volume of peripheral compartment)=7.05×(AGE/10)^1.76(L).The population pharmacokinetics parameters(RSD%) of CL₁,V₁,CL₂, V₂ were 5.04 L·h^-1. (49.6%), 16.1L(29.3%), 0.203 L.h^-1(337.6%),7.05 L(107.7%) respectively. Gender,body surface area, the amoun ofalkalization before MTX infusion have statistic influence on CL₁ and agehas statistic influence on CL₂ and V₂ (P＜0.01).[Conclusion] A good fitness is derived from the PPK that could provideservice for MTX treatment and reduce adverse effects.