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Vortioxetine is a novel anti-major depression disorder drug with a high safety profile compared with other similar drugs. However, little research has been done on drug-drug interactions (DDI) about vortioxetine. In this paper, the inhibitory effect of vortioxetine on cytochrome P450 (CYP450) and the type of inhibitory mechanism were investigated in human and rat liver microsomes. We set up an in vitro incubation system of 200 µL to measure the metabolism of probe substrates at the present of vortioxetine at 37°C. The concentrations of the metabolites of probe substrates were all measured by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. It was found no time-dependent inhibition (TDI) of vortioxetine through determination of half-maximal inhibitory concentration (IC50) shift values. The enzymes and metabolites involved in this experiment in human and rats were as follows: CYP3A4/CYP3A (midazolam); CYP2B6/CYP2B (bupropion); CYP2D6/CYP2D (dextromethorphan); CYP2C8/CYP2C-1 (amodiaquine); CYP2C9/CYP2C-2 (losartan); and CYP2C19/CYP2C-3 (mephenytoin). We found that vortioxetine competitively inhibited CYP2C19 and CYP2D6 in human liver microsomes (HLMs) with inhibition constant (Ki) values of 2.17 µM and 9.37 µM, respectively. It was noncompetitive inhibition for CYP3A4 and CYP2C8, and its Ki values were 7.26 µM and 6.96 µM, respectively. For CYP2B6 and CYP2C9, vortioxetine exhibited the mixed inhibition with Ki values were 8.55 µM and 4.17 µM, respectively. In RLMs, the type of vortioxetine inhibition was uncompetitive for CYP3A and CYP2D (Ki = 4.41 and 100.9 µM). The inhibition type was competitive inhibition, including CYP2B and CYP2C-2 (Ki = 2.87 and 0.12 µM). The inhibition types of CYP2C-1 and CYP2C-3 (Ki = 39.91 and 4.23 µM) were mixed inhibition and noncompetitive inhibition, respectively. The study of the above mechanism will provide guidance for the safe clinical use of vortioxetine so that the occurrence of DDI can be avoided. [ABSTRACT FROM AUTHOR]

Aerosol lidar network can play an important role on revealing structural characteristics of atmospheric boundary layer, urban heat island effect, spatial distribution of aerosols, especially monitoring atmospheric pollution in a megacity. To fulfill the need of monitoring and numerical forecast of atmospheric pollution, an aerosol lidar network is proposed by China Meteorological Administration, which serves as an important part of "MegaCity Experiment on Integrated Meteorological Observation in China" (MEMO). To ensure high standard of data quality and traceability of measurement error, an inter-comparison campaign, dedicated for quality assessment of lidar systems from different institutes and manufacturers, was designed and performed at Beijing Southern Suburb Observatory in September 2021. Six Mie-Rayleigh lidar systems at 1064 nm were involved in this campaign. The strategies for lidar self-evaluations and inter-comparisons were predefined. A lidar system at 1064 nm, which was developed by Atmospheric Remote Sensing group at Wuhan University, was selected as the reference lidar system after passing all self-evaluations quality checks in a strict way. The reference lidar system serves as the corner stone for evaluating the performance of other lidar systems. After using the self-test of Rayleigh fit and signal-to-noise evaluation for each individual lidar system to fast check the data quality, the range-corrected signal and backscatter coefficient obtained from all the lidar systems were inter-compared with a reference lidar system. In the end, the lidar systems were quality assured, of which the standard deviation of range-corrected signal can be controlled within 5% at 500-2000m while 10% at 2000-5000m. For the derived aerosol backscatter coefficients, standard deviations can be controlled within 10% at 500-2000m and 2000-5000 m. The quality assurance strategy lays down a solid basis for atmospheric lidar at near-infrared wavelength and will be applied in Chinese lidar network development. [ABSTRACT FROM AUTHOR]