The DDE model successfully described the non-linear pharmacokinetics of VPA. Furthermore, the proposed population pharmacokinetic model of VPA can be used to design rational dosage regimens to achieve desirable serum concentrations.

A PPK model was developed to estimate the individual clearance in inpatients receiving intravenously infused VCM and could be used to develop individualised dosing of adult Chinese PCM patients.

A PPK model was developed to estimate the individual clearance for patients taking VPA and could be applied for individualizing doses in the target population.

Background: Oxcarbazepine (OXC) is almost completely metabolized to its10-monohydroxy derivative (MHD), which is responsible for the pharmacological effects of the drug. Several studies have described the population pharmacokinetics (PPK) of MHD in pediatric patients, but little is known about its pharmacokinetics in adult patients. In addition, no study to date has proposed a model to investigate the influence of genetic polymorphisms on MHD pharmacokinetics. The aim of this study was to establish a PPK model of MHD to investigate the effects of genetic polymorphisms in UGT2B7, UGT1A9, ABCB1, and ABCB2 in adult Chinese patients with epilepsy and to develop a new dosage guideline for OXC. Methods: Data were prospectively collected from 187 adult patients with epilepsy who were taking OXC. MHD trough concentrations were detected by enzyme-multiplied immunoassay. Patients were genotyped for 4 single nucleotide polymorphisms (UGT2B7 802T>C, UGT1A9 I399C>T, ABCB1 3435C>T, and ABCB2 1249G>A). Other covariates included sex, age, body weight (BW), hepato-renal function, and concomitant medications. Data were analyzed using the nonlinear mixed effects modelling software. Results: The apparent clearance (CL) of MHD was significantly influenced by glomerular filtration rate and BW, and was unrelated to other covariates such as genetic polymorphisms and coadministration with levetiracetam, lamotrigine, and topiramate. Moreover, a new dosage guideline was proposed based on the final model to individualize OXC regimens for adult patients with varying BW and renal function. Conclusions: Glomerular filtration rate was first found as an important covariate influencing MHD CL. A PPK model was established to estimate the individual MHD CL for adult patients taking OXC and may be applied for individualizing doses in the target population.

Introduction: Drug-induced acute kidney injury (D-AKI) is one of the important types of AKI. The incidence of D-AKI in China has rarely been studied. Objective: This study aims to explore the disease burden, related drugs, and risk factors of D-AKI. Methods: A nationwide cross-sectional survey was conducted in adult patients from 23 academic hospitals in 17 provinces in China. Suspected AKI was screened based on serum creatinine changes in accordance with the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for AKI, patients who met the diagnosis of hospital-acquired AKI in January and July of 2014 were defined. Suspected AKI was firstly evaluated for the possibility of D-AKI by pharmacists using the Naranjo Scale and finally defined as D-AKI by nephrologists through reviewing AKI clinical features. Results: Altogether 280,255 hospitalized patients were screened and 1,960 cases were diagnosed as hospital-acquired AKI, among which 735 cases were defined as having D-AKI (37.50%, 735/1,960) with an in-hospital mortality rate of 13.88% and 54.34% of the survivors did not achieve full renal recovery. 1,642 drugs were related to AKI in these patients. Anti-infectives, diuretics, and proton pump inhibitors were the top 3 types of drugs relevant to D-AKI, accounting for 66.63% cumulatively. Besides age, AKI staging, severe disease, hypoalbuminemia, plasma substitute, and carbapenem related D-AKI were independent risk factors for in-hospital mortality of D-AKI patients. Conclusion: In China, D-AKI has caused a substantial medical burden. Efforts should be made to pursue nephrotoxic drug stewardship to minimize attributable risk and improve the prevention, diagnosis, and treatment of D-AKI.