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• W2028766089 abstract "Objective: This study aimed to develop a population pharmacokinetic model for high-dose methotrexate (MTX), specifically focusing on the drug urinary excretion process. Methods and results: Three hundred and forty-eight serum samples and 416 urine samples from 51 Japanese adult patients with malignancies were concurrently fitted into a multi-compartment model using the nonmem program. In the final model, creatinine clearance (CCR, mL/min) and the MTX dose (DOSE10G; 0 when <10 g, 1 when ≥10 g) were the most significant factors that affected the renal clearance (CLr) and non-renal clearance (CLnr), respectively: CLr(L/h) = 5·57 × (CCR/80·0)0·112, V1(L) = 26·9, Q(L/h) = 0·0778, V2(L) = 2·27, CLnr(L/h) = 0·567 × 3·39DOSE10G, where V1 and V2 are the volumes of distribution of the central and peripheral compartments, respectively, and Q is the inter-compartmental (central–peripheral) clearance. For another nine patients, the model enabled a satisfactory Bayesian estimation using two time-point serum concentrations. Conclusion: The newly developed population pharmacokinetic model should improve the quality of serum concentration monitoring of high-dose MTX to predict and control toxic events." @default.
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• W2028766089 date "2008-12-01" @default.
• W2028766089 modified "2023-09-23" @default.
• W2028766089 title "Population pharmacokinetics of high-dose methotrexate in Japanese adult patients with malignancies: a concurrent analysis of the serum and urine concentration data" @default.
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• W2028766089 doi "https://doi.org/10.1111/j.1365-2710.2008.00966.x" @default.
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