Voriconazole
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
In a well-established murine model of disseminated candidiasis with C. albicans, the ratio of the 24-hour area under the free drug concentration-time curve to the minimum inhibitory concentration (AUC:MIC) was the parameter most linked to organism kill, with a mean target ratio of 24 (Andes et al., 2003). This is virtually identical to a proposed target ratio for A. fumigatus of 25, derived from a combination of in vitro, in vivo, and clinical data. (Siopi et al., 2014) The authors proposed a second, surrogate target that could be easier in practice to measure, which is a trough/MIC concentration ratio of 2. An earlier in vitro study found a target AUC:MIC of 38 for A. fumigatus, but higher target ratios of 53 and 72 were needed for A. flavus and A. terreus, respectively, emphasizing that targets may not be not uniform across species. (Al-Saigh et al., 2012) Recently, a novel pharmacokinetic-pharmacodynamic (PK-PD) target has been proposed using serum galactomannan as a surrogate for Aspergillus infection (Huurneman et al., 2016). Using 261 voriconazole and 33 galactomannan measurements from 12 children, the authors determined in a retrospective analysis that a 24-hour voriconazole steady-state AUC:EC50 ratio was significantly associated (P = 0.003) with the terminal galactomannan, where EC50 is the concentration of voriconazole required in an individual patient to obtain half-maximal decline in galactomannan (Huurneman et al., 2016). They chose EC50 because it is an in vivo measure of drug potency, which takes into account patient factors (e.g. immune function) and pathogen factors (e.g. MIC). Both AUC and EC50 can be estimated from measured plasma voriconazole and serum galactomannan.
Clinical Pharmacology Efficacy Studies
Scott Patterson, Byron Jones in Bioequivalence and Statistics in Clinical Pharmacology, 2017
where E is the effect being modelled, E0 is the effect observed without any drug present, C is the concentration of drug in the effect compartment, EC50 is the concentration needed to cause a 50% response, and Emax is the maximum effect that can occur with drug treatment. This is a nonlinear (in concentration) additive model. If concentration is not related to effect, Emax and EC50 would be zero.
Synthesis, Enzyme Localization, and Regulation of Neurosteroids
Sheryl S. Smith in Neurosteroid Effects in the Central Nervous System, 2003
Note: The human GABAR subunit combinations were recombinantly expressed in Xenopus oocytes and measured by two-electrode voltage clamp recordings. GABA was bath applied at an EC10 concentration, and EC50 is the concentration of the steroid required for 50% of the maximum enhancement observed for that receptor. Imax is the maximum potentiation of GABA by the steroid relative to the maximum of GABA alone. ND = not determined.
PEGylated-nanoliposomal clusterin for amyloidogenic light chain-induced endothelial dysfunction
Published in Journal of Liposome Research, 2018
Diana Guzman-Villanueva, Raymond Q. Migrino, Seth Truran, Nina Karamanova, Daniel A. Franco, Camelia Burciu, Subhadip Senapati, Dobrin Nedelkov, Parameswaran Hari, Volkmar Weissig
Data are expressed as mean ± standard error of means with significant p values set at p < 0.05 (two-sided). Maximum dilator response to acetylcholine (10−4 M) and papaverine (10−4 M) were compared between treatment response and baseline control response using paired t-test. Dilator responses between treatments were compared using unpaired t-test. Acetylcholine effective concentration 50% (EC50) is the dose of acetylcholine that produced 50% maximum dilation. EC50 was calculated using nonlinear regression using variable slope (four parameters) and least-squares ordinary fit similar to our previous method (Migrino et al., 2011) using GraphPad Prism 5.0 (GraphPad Software, San Diego CA). EC50 (expressed as LogM) was compared between treatment responses and baseline control responses as well as between treatment responses using paired and unpaired t-test, respectively. Statistical analyzes were also performed using Sigmastat 3.5 (Richmond, CA).
New Multi-Walled carbon nanotube of industrial interest induce cell death in murine fibroblast cells
Published in Toxicology Mechanisms and Methods, 2021
Krissia Franco de Godoy, Joice Margareth de Almeida Rodolpho, Patricia Brassolatti, Bruna Dias de Lima Fragelli, Cynthia Aparecida de Castro, Marcelo Assis, Juliana Cancino Bernardi, Ricardo de Oliveira Correia, Yulli Roxenne Albuquerque, Carlos Speglich, Elson Longo, Fernanda de Freitas Anibal
The cytotoxic activity of OCNT-TEPA was evaluated with the aid of the MTT colorimetric assay (MTT- [3- (4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide] – Sigma-Aldrich, USA) that analyzes the integrity of mitochondrial function through the production of formazan crystals, proportionally, the lower the crystal production, the lower the cell viability (TIM Mosmann 1983). Initially the test was applied to determine which concentrations would be tested, based on the literature, which reported that the most studied concentrations for nanoparticles vary from 1 to 1000 µg/ml. The selection criterion was to use concentrations that proved to be more toxic and nontoxic among those initially tested (1, 10, 50, 100, 250, 500, 750 e 1000 µg/ml). The concentrations of 1, 50, 250, 500 and 1000 µg/ml were chosen to carry out the study. In a 96-well plate, 6 × 03 cells/well were seeded and exposed to OCNT-TEPA. After the exposure period, the wells were washed with PBS (phosphate buffered saline) 1X and the MTT solution (5 mg/ml) was added and the reaction occurred for 4 hours at 37 °C and 5% of CO2. The formazan crystals formed were solubilized with 100 μl of DMSO and the absorbance was measured at 570 nm in a plate spectrophotometer (Thermo Scientific ™ Multiskan ™ GO Microplate Spectrophotometer). From the absorbance data, the EC50 (concentration that induces half the maximum effect) was calculated. The percentage of cytotoxicity occurred by comparing the data obtained with the Control group according to the equation below:
Influence of spray drying on bioactive compounds of blackberry pulp microencapsulated with arrowroot starch and gum arabic mixture
Published in Journal of Microencapsulation, 2020
Gislaine Ferreira Nogueira, Cyntia Trevisan Soares, Luiz Gabriel Pereira Martin, Farayde Matta Fakhouri, Rafael Augustus de Oliveira
The median effective concentration (EC50) is a widely-used parameter to estimate the antioxidant capacity. EC50 is the concentration that inhibits 50% of the DPPH* radicals in solution. The lower the EC50, the higher are the antioxidant activities found (Medina-Torres et al. 2016). As can be seen in Table 1, all samples were able to trap free radicals. Antioxidant activity in powders was significantly (p < .05) influenced by inlet air temperature, which presented negative linear effect and by encapsulating agent concentration, which presented negative linear and quadratic effect on high antioxidant activity determined by the DPPH assay (Table 2). Therefore, blackberry powders with high antioxidant capacity were produced with inlet air temperatures values and encapsulating agent concentration minimum and maximum tested (Figure 4(D)), following the same behaviour as the FRAP assays.
Related Knowledge Centers
- Ic50
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- Potency
- Dose–Response Relationship
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- Hill Equation
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