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Aims Methods Results Conclusions Hydroxychloroquine (HCQ) is recommended for the long‐term treatment of rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. Given the complex process of HCQ metabolism and individual physiological differences, the metabolic profile of HCQ after long‐term administration is unknown. This study aimed to establish a population pharmacokinetic model for long‐term HCQ treatment in patients with rheumatic diseases and to identify the factors influencing HCQ metabolism.This study included 274 HCQ whole‐blood trough concentration data points from 203 patients with rheumatic diseases, all of whom had taken HCQ for more than 6 months, with a median duration of 36 months. A nonlinear mixed‐effects model was derived to establish a population pharmacokinetic model, and potential influencing factors were investigated. Different covariates were used to simulate the optimal dose.The final model describing the HCQ blood concentration–time profile was a compartmental model with first‐order absorption. The estimated values for apparent clearance and volume of distribution were 16.4 L/h and 1220 L, respectively. The clearance of HCQ gradually increased with increasing dosing regimens and weight gain. Monte Carlo simulations were used to determine the optimal dosage regimens for patients with different body weights and drug durations. The simulation results revealed that an initial dose of 5 mg/kg was appropriate.We developed a population pharmacokinetic model for long‐term HCQ therapy in patients with rheumatic diseases. HCQ clearance from whole blood increased progressively with increasing duration of drug administration. [ABSTRACT FROM AUTHOR]

Background: Diffusion tensor imaging (DTI) studies have demonstrated white matter (WM) abnormalities in patients with temporal lobe epilepsy (TLE). However, alterations in the topological properties of the WM structural network in patients with TLE remain unclear. Graph theoretical analysis provides a new perspective for evaluating the connectivity of WM structural networks. Methods: DTI was used to map the structural networks of 18 patients with TLE (10 males and 8 females) and 29 (17 males and 12 females) age‐ and gender‐matched normal controls (NC). Graph theory was used to analyze the whole‐brain networks and their topological properties between the two groups. Finally, partial correlation analyses were performed on the weighted network properties and clinical characteristics, namely, duration of epilepsy, verbal intelligence quotient (IQ), and performance IQ. Results: Patients with TLE exhibited reduced global efficiency and increased characteristic path length. A total of 31 regions with nodal efficiency alterations were detected in the fractional anisotropy_ weighted network of the patients. Communication hubs, such as the middle temporal gyrus, right inferior temporal gyrus, left calcarine, and right superior parietal gyrus, were also differently distributed in the patients compared with the NC. Several node regions showed close relationships with duration of epilepsy, verbal IQ, and performance IQ. Conclusions: Our results demonstrate the disruption of the WM structural network in TLE patients. This study may contribute to the further understanding of the pathological mechanism of TLE. [ABSTRACT FROM AUTHOR]