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The PK/PD cut-off (PK/PDCO) value of florfenicol for calf pathogens was determined for long acting formulations (MSD Nuflor® and a bioequivalent generic product). PK/PDCO is one of the three MICs considered by VetCAST, a sub-committee of the European Committee on Susceptibility Testing (EUCAST), to establish a Clinical Breakpoint for interpreting Antimicrobial Susceptibility Testing (AST). A population model was built by pooling three pharmacokinetic data sets, obtained from 50 richly sampled calves, receiving one of two formulations (the pioneer product and a generic formulation). A virtual population of 5,000 florfenicol disposition curves was generated by Monte Carlo Simulations (MCS) over the 96 h of the assumed duration of action of the formulations. From this population, the maximum predicted MIC, for which 90% of calves can achieve some a priori selected critical value for two PK/PD indices, AUC/MIC and T>MIC, was established. Numerical values were established for two bacterial species of the bovine respiratory disease (BRD) complex, Pasteurella multocida and Mannheimia haemolytica. It was concluded that the PK/PDCO of florfenicol for both AUC/MIC and T>MIC was 1 mg/L.
Pubmed ID: 31244816
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A second-generation retrovirus producer lines for the generation of helper free ecotropic and amphotropic retroviruses. The lines are based on the 293T cell line (a human embryonic kidney line transformed with adenovirus E1a and carrying a temperature sensitive T antigen co-selected with neomycin). The unique feature of this cell line is that it is highly transfectable with either calcium phosphate mediated transfection or lipid-based transfection protocols-- up to 50% or higher of cells can be transiently transfected. The lines were created by placing into 293T cells constructs capable of producing gag-pol, and envelope protein for ecotropic and amphotropic viruses. The lines offered advantages over previous stable systems in that virus can be produced in just a few days. Academic and non-profit laboratories may obtain the Phoenix cells from either Allele Biotechnology or the National Gene Vector Bank. The vectors may be obtained from Addgene. They are no longer distributing these reagents from the lab.
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