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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Dactinomycin was the first Streptomyces-derived antibiotic to be shown to have antitumor activity. It was initially developed as a potent bacteriostatic agent, although it was later found to be too toxic for general use. The antitumor activity of this agent did not emerge until ten years later when it was tried with great success to treat Wilm’s tumor (a kidney tumor in children) and a type of uterine cancer. It was approved by the FDA in the US in 1964 and launched by Merck Sharp and Dohme (MSD) under the trade name CosmegenTM.
Pharmacokinetic/Pharmacodynamic Modeling of Antibiotics
Published in Hartmut Derendorf, Günther Hochhaus, Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
Arno Nolting, Hartmut Derendorf
The introduction of a bacteriostatic agent into a balanced culture of E. coli results in a new and lower apparent generation rate constant kapp. Since the mode of action for bacteriostatic drugs is the inhibition of growth rather than kill, the resulting kapp will be positive. If the effect of the antibiotic is concentration-dependent, the resulting kapp will be smaller for higher drug concentrations. Garrett8 found four patterns of interaction between drug concentration and kapp (class I to IV interactions).
The Pharmacist Role in Antimicrobial Stewardship and Interpreting Microbiology Laboratory Results
Published in Nancy Khardori, Bench to Bedside, 2018
Stephanie Crosby, Mark DeAngelo, Nancy Khardori
The mechanism of action or activity of the agent being initiated also needs to be considered. Some antibiotics are bactericidal whereas some may be bacteriostatic. Bactericidal agents will kill the bacteria by disrupting the cell membrane, cell wall or the cellular DNA (Nemeth et al. 2015). Examples of antibiotics in the category include beta-lactams, fluoroquinolones and glycopeptides. Agents that prevent further bacterial replication versus killing the organism are considered bacteriostatic. Antibiotics that are bacteriostatic include macrolides and lincosamides. In severe infections, such as meningitis or endocarditis a bacteriostatic agent would not be ideal as more aggressive killing would favor a better clinical outcome.
Optimization of dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin against methicillin-resistant Staphylococcus aureus in neutropenic patients with cancer by Monte Carlo simulations
Published in Journal of Chemotherapy, 2021
Xiaochen Wei, Mingfeng Zhao, Xia Xiao
Linezolid, the first oxazolidinone, is an important therapeutic option for infections caused by resistant Gram-positive bacterial pathogens. Currently, there is controversy regarding the use of linezolid in patients with neutropenic because it is a bacteriostatic agent.23 Our simulation results suggested that the standard linezolid dosage (1200 mg/day) was appropriate against S.aureus with an MIC of 1 µg/mL at the AUC0-24/MIC index of ≥ 80 in neutropenic patients with cancer, and as the AUC0-24/MIC index increased from 80 to 120, the corresponding PTA decreased from 91.00% to 73.28%. For an MIC of 2 µg/mL, none of the simulated dosing regimens of linezolid could achieve a PTA value of ≥ 90% against S.aureus. Furthermore, CFRs of several linezolid simulated dosing regimens reached < 80% against MRSA at the AUC0-24/MIC values of 80-120, indicating a lower success probability for infection in neutropenic patients with cancer. These results were similar to a previous PK/PD study report that linezolid dosing regimens (600 mg q8h or 600 mg q6h) applied to MRSA did not achieve CFRs > 80% in critically ill patients, and so an in-depth optimisation strategy for the dosing regimen needs to be considered for patients infected by MRSA. In addition, one should acknowledge that reports of myelosuppression could be a potential limitation for the use of linezolid in neutropenic patients with cancer.23
Qualitative risk assessment of follicle stimulating hormone injectable products
Published in Expert Opinion on Drug Delivery, 2020
Douglas T Steinke, Osman H Zarroug, Raj Mathur, Helen Kendrew, Julian Jenkins
The provision of pre-filled syringes of solvent with the multi-use HMG vial was considered an advantage over the single-use HMG vial products because it avoided the need to snap open a glass ampoule of solvent. The Menopur® multidose product comes as a fully prepared kit with all accessories included in the package. However, its preparation and administration still requires multiple needle manipulations and for this reason, similar to single-use HMG vials, the overall risk for sharps injury was assessed as medium. Furthermore, the multidose vials could theoretically pose a risk of contamination as a result of multiple uses, even though a bacteriostatic agent is included in the formulation [13]. Importantly, each Menopur® multidose vial is intended for use in a single patient, and infection control guidelines advise against the use of multidose vials for multiple patients, as they carry a high risk of contamination and cross-infection [16].
Sustained release and pharmacologic evaluation of human glucagon-like peptide-1 and liraglutide from polymeric microparticles
Published in Journal of Microencapsulation, 2019
Luis Peña Icart, Fernando Gomes de Souza, Luís Maurício T. R. Lima
The kinetic release of peptide from loaded-microparticles was performed as described elsewhere (Guerreiro et al.2012). In brief, microparticles containing an estimated amount of 1 mg of peptide were dispersed in 2 mL of phosphate buffer pH 7.2 and 100 mM of NaN3, an anti-microbial agent that inhibit microbial growth, acting as a bacteriostatic agent by inhibiting cytochrome oxidase in gram-negative and gram-positive bacteria). Then 200 µl of the same microparticles suspension were placed in eppendorf tubes. The tubes were sealed and left under orbital agitation (150 rpm) at 37 °C. At the indicated time interval (0, 1 h, 24 h, 48 h, 4d, 8d, 15d, 20d, 25d, 30d and 45d) the tubes were removed from the shaker and they were centrifuged at 5,000 rpm at 4 °C for 15 min, the supernatant was transferred to another eppendorf tube, flash frozen and kept at -20 °C until use. Total peptide release was inferred by quantification by the fluorescamine method as described above.