What is known and objectives Augmented renal clearance (ARC) is characterized by enhanced renal clearance, which leads to insufficient vancomycin exposure and treatment failure. In haematologic malignancy patients, determination of optimal vancomycin dosage is essential because of high stake of life‐threatening bacterial infection and increased clearance. The aim of this study was to describe vancomycin pharmacokinetic parameters in haematologic malignancy with augmented renal clearance children and define the appropriate dosing regimen to achieve an AUC0‐24h/MIC ≥400. Methods Hematologic malignancy with ARC children was enrolled in this retrospective study. The vancomycin PPK model was established by non‐linear mixed‐effects modelling programme. Goodness‐of‐fit (GOF) plots, non‐parametric bootstrap, normalized prediction distribution error (NPDE) and visual predictive checks (VPCs) were carried out for internal evaluation of the final model. Monte Carlo simulation method was used to stimulate the optimal dosage regimens. Results Fifty‐three patients with 106 samples were included. A one‐compartment model with first‐order elimination was developed, and the final model was as follows: CL (L/h) = 6.32×（WT/70）0.75 × e0.0467; V(L) = 39.6×(WT/70), where WT denotes weight (kg). The internal validation of the model showed a good prediction performance. Monte Carlo simulation results showed that when MIC was 0.5 mg/L or 1 mg/L, the recommended doses to achieve a target of AUC0‐24h/MIC ≥400 were 25 to 40 and 50 to 75 mg/kg/d, respectively. With decreasing weight, the recommended dosage to achieve an AUC0‐24h/MIC ≥400 increased. What is new and conclusion A one‐compartment vancomycin PPK model was established in haematologic malignancy with augmented renal clearance children with weight with allometric scaling as a significant covariate. When MIC was 1 mg/L, current recommended paediatric dosages were insufficient in haematologic malignancy with augmented renal clearance children and should be increased.

What is known and objectives: Some previous studies have indicated that serum cystatin C (Cys C) is a better marker than serum creatinine (SCR) for assessing the glomerular filtering rate (GFR). However, in almost all population pharmacokinetic models of vancomycin, the GFR is usually estimated from SCR. Therefore, the aim of this study was to compare the GFR estimated from SCR (sGFR) with the GFR estimated from Cys C (cGFR) and investigate which one can describe the characteristics of vancomycin population pharmacokinetics better in Chinese neurosurgical adult patients. Methods: Patients from the Neurosurgery Department aged ≥18 years were enrolled retrospectively. Among these patients, the data from 222 patients were used to establish two population pharmacokinetic models based on sGFR and cGFR, separately. The data from another 95 patients were used for the external validation of these two models. Non-linear mixed-effect modelling (NONMEM) 7.4.3 was used for the population pharmacokinetic analysis. Results: We developed two one-compartment models with first-order absorption based on Cys C and SCR, separately. In the Cys C model, age, body weight and cGFR were significant covariates on the clearance rate (CL) of vancomycin (typical value, 6.4 L/hour). In the SCR model, age and sGFR were significant covariates on the CL (typical value, 6.46 L/hour). The external validation results showed that the predictive performance of the two models was similar. What is new and conclusion: In this study, the predictive performance of two models was similar in neurosurgical patients. We did not find a significant improvement in the predictive performance of the model when GFR was estimated from Cys C.

Background: Hematopoietic stem cell transplantation (HSCT) is an effective treatment for hematological disorders. Tacrolimus is widely used after HSCT, but it has highly interindividual variable pharmacokinetics. Population pharmacokinetics (PPK) researches of tacrolimus in children with β-thalassemia major (β-TM) undergoing HSCT are insufficient. Objective: To establish a PPK model of tacrolimus in children with β-TM and optimize initial dosing regimen for achieving target concentration of 5 to 15 ng/mL. Methods: Data on patients aged <18 years were retrospectively collected from January 2017 to December 2018. PPK analysis and Monte Carlo simulations were performed using nonlinear mixed-effects modeling. Results: A data set of 55 patients with 332 concentrations was included. A 2-compartment model could best describe the pharmacokinetics of tacrolimus. The body surface area and gender were significant covariates in the final model. The typical value of clearance, the distribution volume of the central room, the distribution volume of the peripheral room, and the intercompartmental clearance were 5.05L/h, 4.33L, 155L, and 6.22L/h, respectively. The optimal initial dosing regimen of 0.03, 0.04, 0.05, 0.06, and 0.10 mg/kg were appropriate for female children with a weight (WT) of 50 to 10 kg. The regimen of 0.04, 0.05, 0.06, 0.07, and 0.12 mg/kg is suitable for male children with a WT of 50 to 10 kg. The probability of target attainment (PTA) of each regimen reached 91%. Conclusion and Relevance: A stable PPK model of tacrolimus was established. The proposed dosage regimen reached a good PTA, which could provide a reference for tacrolimus therapy.