High-dose methotrexate (HD-MTX) is widely used in pediatric acute lymphoblastic leukemia (ALL) treatment regimens. In this study, we aimed to develop a population pharmacokinetic (PK) model of HD-MTX in Chinese pediatric patients with ALL for designing personalized dosage regimens. In total, 4,517 MTX serum concentration data for 311 pediatric patients with ALL, aged 0.75–15.2 years and under HD-MTX treatment, were retrospectively collected at a tertiary Children’s Hospital in China. The non-linear mixed-effect model was used to establish the population PK model, using NONMEM software. The potential covariate effects of age, body weight, and biochemical measurements (renal and liver function) on MTX PK disposition were investigated. The model was then evaluated using goodness-of-fit, visual predictive check. MTX PK disposition was described using a three-compartment model reasonable well. Body weight, implemented as a fixed allometric function on all clearance and volume of distribution parameters, showed a substantial improvement in model fit. The final population model demonstrated that the MTX clearance estimate in a typical child with body weight of 19 kg was 6.9 L/h and the central distribution of volume estimate was 20.7 L. The serum creatinine significantly affected the MTX clearance, with a 0.97% decrease in clearance per 1 μmol/L of serum creatinine. Other covariates (e.g., age, sex, bilirubin, albumin, aspartate transaminase, concomitant medication) did not significantly affect PK properties of MTX. The proposed population PK model could describe the MTX concentration data in Chinese pediatric patients with ALL. This population PK model combined with a maximum a posteriori Bayesian approach could be used to estimate individual PK parameters, and optimize personalized MTX therapy in target patients, thus aiming to reduce toxicity and improve treatment outcomes.

This review concludes that body weight and age were the most important factors associated with the clearance of theophylline in paediatric patients. Body weight, age and smoking were most frequently used to estimate the clearance of theophylline in adults. Future studies are warranted to detect the influence of new factors, such as cytochrome P450 (CYP) 1A2 gene polymorphisms, on the pharmacokinetics of theophylline because some pharmacokinetic variability was not fully explained.

-Using a community-based population cross-sectional study, we investigated the validity of an enzymatic method for glycated albumin (GA) measurements and evaluated its utility as a diagnostic tool for diabetes mellitus (DM). In total, 1,211 participants from the city of Harbin, People's Republic of China, were enrolled in the study. A receiver operating characteristic (ROC) analysis for GA, fasting plasma glucose (FPG) and haemoglobin A 1c (HbA 1c ) measurements in diagnosed and undiagnosed DM were compared, based on a definition of DM using 1999 WHO criteria. We also estimated the correlation among GA, HbA 1c and other clinical characteristics. Significant and positive correlations of fasting serum GA with FPG (rϭ0.8097) and HbA 1c (rϭ0.8976) were found in participants enrolled in the study. ROC analysis for GA predicting undiagnosed DM with a cut-off point of 15.7% was similar to that of FPG and HbA 1c . Therefore, our data indicate that GA is a potential tool for DM diagnosis.

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