抄録
Pharmacokinetic analysis was carried out with respect to the methotrexate (MTX) serum concentration. Nine patients (26 instillations) undergoing MTX therapy were investigated. Better correlation was shown between the MTX serum concentration and the dose per body surface area (BSA) as compared with the dose per body weight (BW) or the dose per ideal body weight (IBW).
Analysis of the data of the MTX serum concentration involved a 2-compartment open model (2-com) to determine four parameters (K21, α, β and Vd) with respect to each instillation. As a result of the analysis, an extremely high correlation was observed between the calculated and the measured concentrations. To examine the effects of age and dose on the pharmacokinetic parameters, we divided the data into two groups: low-dose (<4000mg/m2) adult (≥15) group (LA group) and high-dose (≥4000mg/m2) child (<15) group (HC group).
Population pharmacokinetic parameters were calculated by standard two-stage (STS) method for the LA and HC groups, respectively. Significant differences were detected with respect to K12, K21 and β between the LA and HC groups. For an adult administered a high-dose of MTX, his/her parameters belonged to the values of the HC group. On the other hand, when a child was administered a low dose of MTX, his/her parameters belonged to the values of the LA group. Therefore, K12, K21 and β are considered to be determined only by the dose and not by the age.
