ADMET and DMPK最新文献

Novel Ag(I) complexes (2a-2c) with phenolic Schiff bases were synthesized using 4,6-di-tert-butyl-3-(((5-mercapto-1,3,4-thiadiazol-2-yl)imino)methyl)benzene-1,2-diol (1a), 4,6-di-tert-butyl-3-(((4-mercaptophenyl)imino)methyl)benzene-1,2-diol (1b), and 4,6-di-tert-butyl-3-(((3-mercaptophenyl)imino)methyl)benzene-1,2-diol (1c). They were examined by elemental analysis, FT-IR, UV-Vis, ¹H-NMR spectroscopy, XRD, cyclic voltammetry, conductivity measurements, and biological methods. The complexes are characterized by distorted geometry of the coordination cores AgN₂S₂ (2c), AgNS (2b) and AgS₂ (2a). These stable complexes were not typified by the intramolecular redox reaction in organic solvents resulting in the formation of silver nanoparticles (AgNPs). Antibacterial activity of 1a-1c and 2a-2c was evaluated in comparison with AgNPs and commonly used antibiotics. All the complexes were more active than the ligands against the bacteria tested (14), but they were less active than AgNPs and commonly used antibiotics. Both 1a-1c and their complexes 2a-2c exhibited the capability for the bovine heart Fe(III)-Cyt c reduction. The ligands 1b and 1c were characterized by the highest reduction rate among the compounds under study, and they showed a higher reducing ability (determined by cyclic voltammetry) as compared with that of their Ag(I) complexes 2b and 2c.

Antibiotic-resistant Escherichia coli infection of poultry causes significant economic losses. Extended spectrum β lactamases (ESBL) producing E. coli was inoculated in a broiler, Rhode Island Red and Haringhata Black birds orally at 56×10⁸ c.f.u. mL^-1 for induction of diarrhoea. Pharmacokinetics of ceftriaxone-tazobactam combination (8:1) was studied following a single intramuscular injection at 28.125 mg kg^-1 and the combination was administered twice daily to treat such infection. Plasma concentration of both ceftriaxone persisted up to 8 h in experimental birds and maintained an approximate ratio of 8:1 with tazobactam for a period of 2 h, 0.25 h and 0.75 h, respectively in a broiler, Rhode Island Red and Haringhata Black birds. The K _el was significantly lower in all experimental birds compared to healthy birds. Efficacy study was conducted in diarrhoeic birds by administration of ceftriaxone-tazobactam combination at 28.125 mg kg^-1 body weight twice daily intramuscularly for three days which caused an increase in specific antibody titre in the broiler on 5^th day and in Rhode Island Red birds 10^th day. However, Haringhata black birds were inherently showed more resistance towards the infection. The combination of ceftriaxone and tazobactam in the ratio of 8:1 can be an effective treatment to combat ESBL producing E. coli infections.

Recently, the rapid increase in antibiotic-resistant pathogens has caused serious health problems. Researchers are searching for alternative antimicrobial substances to control or prevent infections caused by pathogens. Different strategies are used to develop effective antibacterial agents, and in this respect, nanoparticles are undoubtedly promising materials. Nanoparticles act by bypassing drug resistance mechanisms in bacteria and inhibiting biofilm formation or other important processes related to their virulence potential. Nanoparticles can penetrate the cell wall and membrane of bacteria and act by disrupting important molecular mechanisms. In combination with appropriate antibiotics, NPs may show synergy and help prevent the developing global bacterial resistance crisis. Furthermore, due to characteristics such as enhanced biocompatibility and biodegradability, polymer-based nanoparticles enable the development of a wide range of medical products. Antibacterial applications of nanoparticles range from antimicrobial synthetic textiles to biomedical and surgical devices when nanoparticles are embedded/loaded/coated into different materials. In this review, the antibacterial mechanisms of nanoparticles and their potential for use in the medical field are discussed.

The purpose of the present study was to evaluate the predictability of PAMPA for the effect of metal ions on the bioavailability of fluoroquinolones (FQ). Eleven FQs and seven metal ions were employed in this study. The PAMPA membrane consisted of a 10 % soybean lecithin (SL) - decane solution. A drug solution in MES buffer with or without a metal ion (added as a chloride salt) was added to the donor compartment. In the absence of metal ions, FQ showed relatively high permeability (> 5 × 10^-6 cm/sec) in SL-PAMPA despite their hydrophilic and zwitterionic properties. As the PAMPA permeability ratio with/without metal ions became smaller, the urinary excretion and AUC ratios tended to be smaller, suggesting that SL-PAMPA is a suitable in vitro model to evaluate the potential effect of metal ions on the bioavailability of FQ. However, the reduction in AUC and urinary excretion was overestimated for low solubility metal ion formulations (dried aluminum hydroxide gel and La₂(CO₃)₃・8H₂O). In such cases, the dissolution of the metal ion formulations and the permeation of FQs should be simultaneously evaluated.