Sulfonamides
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
The degree of sulfonamide protein binding influences the rate of renal excretion of these drugs (see section 5d, Excretion). The protein-bound drug does not penetrate into some body compartments, such as the subarachnoid space, but this may not apply if the meninges are inflamed. Madsen et al. (1963) compared the sulfonamide concentration and the antibacterial activity in serum of two long-acting sulfonamides (sulfadimethoxine and sulfamethoxypyridazine) with sulfadiazine. These authors found that these three sulfonamides all produced about the same antibacterial activity in the serum. There appeared to be a close correlation between the total sulfonamide concentration and the antibacterial activity regardless of the degree of protein binding. The highly protein-bound long-acting sulfonamides also penetrated well into extravascular fluids and exudates, particularly when these were of a high protein content. There are many considerations in assessing the effect of protein binding on antibacterial activity (Rolinson, 1980). A protein-bound drug is essentially without antibacterial effect and is nondiffusible, but this is only a temporary state, because when a protein-bound drug dissociates, the drug is available again in active form. The free unbound plasma levels of a drug dictate the free levels in extravascular fluids. The level of free drug after therapeutic doses and how this relates to the MIC of the organism are important factors in determining therapeutic efficacy.
Supercritical Fluid Extraction as a Sample Preparation Tool in Analytical Toxicology
Steven H. Y. Wong, Iraving Sunshine in Handbook of Analytical Therapeutic Drug Monitoring and Toxicology, 2017
Parks and Maxwell63 recognized this problem during a study of the SFE of three sulfonamide drugs from chicken tissues. In this investigation, recoveries from three tissues (liver, breast, and thigh) were compared. Tissues were fortified with the sulfonamides (sulfamethazine, sulfadimethoxine, and sulfaquinoxaline), mixed with Hydromatrix (Celite 566), and extracted with pure SF-CO2 at 40°C and 68 MPa. The drugs and co-extracted endogenous material were first collected on off-line alumina SPE columns. Recoveries of the three drugs from the various tissue sites are listed in Table 5–3. The recoveries of all three drugs were low and inconsistent with this off-line collection technique. In addition, sulfonamide peak areas were difficult to integrate because of high background ultraviolet (UV) interferences that may be observed in the HPLC chromatogram shown in Figure 5–6a. Cross et al.90 also isolated sulfonamides from chicken livers using an off-line solvent-trapping system of the type shown in Figure 5–3a. Recoveries were higher than those reported by Parks and Maxwell;63 however, to achieve these recoveries, the researchers increased the polarity of the SF by adding 25% MeOH to the CO2. Incorporation of the MeOH modifier resulted in the need for additional post-SFE clean-up operations to prepare the extract for HPLC analysis. High concentrations of polar modifiers in the SF also limit the choice of off-line collection to solvent trapping, because extracted solutes collected on sorbent beds would be eluted during the extraction process due to the presence of the modifier (Figure 5–6b).
Novel curcumin nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cells
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2023
Steve Harakeh, Saber H. Saber, Rajaa Al-Raddadi, Turki Alamri, Soad Al-Jaouni, Mohammed Qari, Yousef Qari, Shafiul Haque, Ayat Zawawi, Soad S. Ali, Zakaria Y. Abd Elmageed, Shaker Mousa
It has been known that primary cancer cells metastasise to distant organs through degradation of extracellular matrix and promoting cell migration, invasion, and angiogenesis [46]. Different approaches, including nanoformulation, have been undertaken to inhibit cancer metastasis and recurrence. Our results show that treatment of LC with 2.5 to 10 µg/ml of Cur-NPs inhibited cell migration and angiogenesis as evidenced by the results from wound-healing assay and chicken embryo model. Arya et al. reported comparable results of anti-migratory and anti-invasive property when pancreatic cells were treated with PLGA chitosan/PEG curcumin NPs compared to cells treated with native curcumin [42]. The chick embryo and its chorioallantois membrane have been used as an accepted model although its reported limitations for evaluating drug delivery loaded in nanoparticles [47,48]. An investigation performed by de Carvalho et al. examined the effect of curcumin-loaded nanoformulations and their different coating agents using a chick embryo model. They found that curcumin NPs coated with P80, PEG, EUD and CS reduce angiogenic and teratogenic effects in the treated chick embryos [49]. In addition, a study conducted by Dragostin et al. revealed that treatment of chick embryo with chitosan-sulfadimethoxine (CLC) and chitosan-sulfisoxazole (CLD) NPs exerted an antiangiogenic effect [50].
Metabolic map of the antiviral drug podophyllotoxin provides insights into hepatotoxicity
Published in Xenobiotica, 2021
Dongxue Sun, Xiaoxia Gao, Qiao Wang, Kristopher W. Krausz, Zhongze Fang, Youbo Zhang, Cen Xie, Frank J. Gonzalez
The bile samples were separated and analysed using a Waters Acquity UPLC system coupled to a Waters Synapt HDMS Q-TOF mass spectrometer under the following conditions: capillary volts 3 kV, sample cone 40 V, source temperature 150 °C, desolvation temperature 400 °C, cone and desolvation gas flow 50 and 900 L/h, respectively. Data were acquired in centroid mode in both positive and negative electrospray ionization modes, using sulfadimethoxine as the Lock Mass. Mass range acquired was 50–900 Amu at 0.3 second scans. Chromatography was carried out using a Waters Acquity BEH C18 column (2.1 × 50 mm) under acidic conditions using water (A) and acetonitrile (B) containing 0.1% formic acid. The following gradient was used: initial conditions 98% (A) for 0.5 min, to 80% (A) at 6.5 minutes, to 70% (A) at 8.0 min, to 1% (A) at 8.5 min, held for one min, and returned to the initial conditions for two min for column equilibration. Total run time was 11.5 min. Column temperature was maintained at 40 °C. All samples were injected at 5 µL.
Functional assessment of rat pulmonary flavin-containing monooxygenase activity
Published in Xenobiotica, 2019
Yildiz Yilmaz, Gareth Williams, Nenad Manevski, Markus Walles, Stephan Krähenbühl, Gian Camenisch
Benzydamine hydrochloride, benzydamine N-oxide maleate, NADPH, sulfadimethoxine (SDM) and 1-aminobenzotriazole were purchased from Sigma-Aldrich (Poole, UK). HPLC grade water and acetonitrile were purchased from VWR (Leicestershire, UK). Sprague-Dawley rat (pool of 299) lung microsomes were obtained from Xenotech (Kansas City, MO). Lung microsomes were not further characterized with regard to CYP and FMO protein content.
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