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- W3216898889 abstract "Linezolid (LNZ), an oxazolidinone antibiotic, has 100% oral bioavailability and favorable activities against gram-positive pathogens. The in vitro PK/PD model was developed based on concentrations obtained with routine doses in humans can be used to guide dose optimization in the clinic.In this study, we employed an in vitro PK/PD model to simulate the changes in the plasma concentration of linezolid in the human body against a clinical isolate of MRSA in vitro. A high-performance liquid chromatography (HPLC)-UV method was applied to measure the concentration of linezolid. Bacterial samples were collected at different times from the central compartment for count.The chromatographic separation was carried out with an AichromBond-AQC18 column(250mm×4.6mm, 5μm), using a mobile phase of water with 0.1% formic acid:acetonitrile 70:30 (v/v), followed by detection at 254 nm, and a single detection run was completed within 10 min. The method was validated by estimating the precision and accuracy for the inter- and intra-day analyses in the concentration range of 0.25-32 mg/L. The method was linear over the investigated range of 0.125-32 mg/L, with all correlation coefficients R2 = 0.9999. The intra-day and inter-day precisions were within 7.598%, and the method recovery ranged from 90.912% to 106.459%. In vitro PK/PD model, both the absorption and elimination of linezolid being simulated can be precisely controlled by computer. In the control group, the bacterial reached 7.9 Log10CFU/mL in the first 48h and maintained until the end, indicating that the colonies grew well in vitro PK/PD model. In the linezolid 600 mg q12h administration group, the colony decreased to 2.39 Log10CFU/mL at 24h, showing a good bactericidal effect; however, the colonies resumed growth to the initial level in 48h, indicating an emergence of resistance.We successfully established an in vitro infection PK/PD model and developed an HPLC-UV method to determine linezolid concentration for resistance investigation. The results suggest that the 600 mg q12h dosing regimen may no longer be applicable and requires optimization." @default.
- W3216898889 created "2021-12-06" @default.
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- W3216898889 date "2021-12-01" @default.
- W3216898889 modified "2023-09-27" @default.
- W3216898889 title "Development and Validation of an HPLC-UV Method for Quantitation of Linezolid: Application to Resistance Study Using in vitro PK/PD Model" @default.
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- W3216898889 doi "https://doi.org/10.2147/idr.s343200" @default.
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