Despite excellent bactericidal effect, dosing adjustment of polymyxin B for patients with renal insufficiency and polymyxin B-related nephrotoxicity is still a major concern to clinicians. The aim of this study was to compare the population pharmacokinetic (PK) properties of polymyxin B in Chinese patients with different renal function and to investigate the relationship between PK parameters and polymyxin B related-acute kidney injury (AKI). A total of 37 patients with normal renal function (creatinine clearance ≥ 80 mL/min) and 33 with renal insufficiency (creatinine clearance < 80 mL/min) were included. In the two-compartment population PK models, the Cl (2.19 L/h vs 1.58 L/h; P < 0.001) and Q (13.83 L/h vs 10.28 L/h; P < 0.001) values were significantly different between the two groups. The simulated AUCss,24h values for patients with normal renal function were higher than those for patients with renal insufficiency. However, the renal dosing adjustment of polymyxin B seemed not to be necessary. Besides, during the treatment, AKI occurred in 23 (32.86%) patients. The polymyxin B AUCss,24h in patients with AKI was significantly higher than that in patients without AKI (108.66 ± 70.10 mg⋅h/L vs 66.18 ± 34.79 mg⋅h/L; P = 0.001). Both the ROC curve and Logistic regression analysis showed AUCss,24h > 100 mg⋅h/L was a good predictor for the probability of nephrotoxicity.

a b s t r a c tToona sinensis (Juss.) M.Roem, Meliaceae, a deciduous plant native to eastern and southeastern Asia, is widely used in Traditional Chinese Medicine. This paper was aimed to summarize the current advances in traditional usage, phytochemistry, pharmacology and toxicology of T. sinensis. In this review, various types of data of T. sinensis are discussed in the corresponding parts of this paper, and perspectives for possible future studies of this plant are discussed. The main constituents of T. sinensis are terpenoids, phenylpropanoids and flavonoids, etc., and its pharmacological activities include anti-tumor effects, antioxidant activities, anti-diabetic effects and anti-inflammatory effects. Although a series of phytochemical and pharmacological researches of this plant have been conducted, the active constituents and action mechanism of these activities should be also further explored. Furthermore, the present review also indicates that T. sinensis has potentials to develop into drugs for treating various diseases with high efficacy and low toxicity, particularly in cancer, diabetes and inflammatory disorders. In conclusion, the paper provides a full-scale profile of the traditional usage, phytochemistry, pharmacology and toxicology of T. sinensis, and also provides potential therapeutic uses and drug development prospects of this plant.

Polymyxin B is used as a last therapeutic option for the treatment of multidrug-resistant Gram-negative bacterial infections. This study aimed to develop a population pharmacokinetic model and limited sampling strategy, a method to estimate the area under the concentration curve (AUC) by using a limited number of samples, to assist therapeutic drug monitoring of polymyxin B in Chinese patients. Population pharmacokinetic analysis was performed using Phoenix ® NLME with data obtained from 46 adult patients at steady state. Various demographic variables were investigated as potential covariates for population pharmacokinetic modeling. The limited sampling strategies based on the Bayesian approach and multiple linear regression were validated using the intraclass correlation coefficient and Bland-Altman analysis. As a result, the data was described by a two-compartment population pharmacokinetic model. Through the modeling, creatinine clearance was found to be a statistically significant covariate influencing polymyxin B clearance. The limited sampling strategies showed the twopoint model (C 0h and C 2h) could predict polymyxin B exposure with good linear relativity (r 2 > 0.98), and the four-point model (C 1h , C1 .5h , C 4h , and C 8h) performed best in predicting polymyxin B AUC (r 2 > 0.99). In conclusion, this study successfully developed a population pharmacokinetic model and limited sampling strategies that could be applied in clinical practice to assist in therapeutic drug monitoring of polymyxin B in Chinese patients.

Background and ObjectiveTetrandrine (TET) is a bisbenzylisoquinoline alkaloid extracted from Stephania tetrandra Moore. Recent studies have suggested that TET can reduce the inflammatory response in microglia, but the mechanisms remain unclear. The aim of this study is to investigate whether TET can inhibit lipopolysaccharide (LPS)-induced microglial activation and clarify its possible mechanisms.Study Design/Materials and MethodsCell viability assays and cell apoptosis assays were used to determine the working concentrations of TET. Then, BV2 cells were seeded and pretreated with TET for 2 h. LPS was then added and incubated for an additional 24 hours. qRT-PCR and ELISA were used to measure the mRNA or protein levels of IL1β and TNFα. Western blotting was utilized to quantify the expression of CD11b and cell signaling proteins.ResultsTET at optimal concentrations (0.1 µM, 0.5 µM or 1 µM) did not affect the cell viability. After TET pretreatment, the levels of IL1β and TNFα (both in transcription and translation) were significantly inhibited in a dose-dependent manner. Further studies indicated that phospho-p65, phospho-IKK, and phospho-ERK 1/2 expression were also suppressed by TET.ConclusionsOur results indicate that TET can effectively suppress microglial activation and inhibit the production of IL1β and TNFα by regulating the NF-kB and ERK signaling pathways. Together with our previous studies, we suggest that TET would be a promising candidate to effectively suppress overactivated microglia and alleviate neurodegeneration in glaucoma.