Ofloxacin

合成路线和反应条件： 氧氟沙星的合成涉及多个步骤。一种方法包括使 (N,N)-二甲基氨基乙基丙烯酸酯与氨基丙醇在甲苯中反应，然后加入路易斯碱催化剂和三甲基氯硅烷来保护羟基和酰胺基。然后用四氟苯甲酰氯处理反应混合物，然后进行酸洗涤、脱保护基团和有机层浓缩以获得油层。该油层用二甲基甲酰胺和无水氟化钾进一步处理，得到二氟羧酸。 最后，二氟羧酸与 N-甲基哌嗪在二甲基亚砜中，以三乙胺作为酸结合剂在 90-100°C 下反应生成氧氟沙星 .

工业生产方法： 氧氟沙星的工业生产通常涉及使用与上述类似的反应条件进行大规模合成。 该工艺针对高产率和高纯度进行了优化，并对反应参数进行仔细控制，以最大限度地减少杂质并提高合成效率 .

反应类型： 氧氟沙星经历各种化学反应，包括氧化、还原和取代。 例如，它可以在酸性介质中被硫酸铈(IV) 氧化，导致形成不同的氧化产物 .

常用试剂和条件： 氧氟沙星反应中常用的试剂包括用于氧化的硫酸铈(IV)，以及各种有机溶剂，如二甲基甲酰胺和二甲基亚砜。 反应条件通常涉及受控温度和 pH 值，以确保所需的化学转化 .

形成的主要产物： 氧氟沙星氧化形成的主要产物包括各种氧化衍生物，可以使用高效液相色谱和质谱等技术对其进行鉴定和表征 .

Therapeutic Indications

Ofloxacin is indicated for a variety of infections, including:

• Respiratory Tract Infections : Effective in treating community-acquired pneumonia and acute bacterial exacerbations of chronic bronchitis .
• Urinary Tract Infections : Demonstrated high efficacy in treating uncomplicated urinary tract infections caused by susceptible organisms .
• Skin and Soft Tissue Infections : Utilized for treating infections involving the skin and soft tissues .
• Sexually Transmitted Infections : Approved for the treatment of urethral and cervical gonorrhea .
• Ocular Infections : Used in ophthalmic solutions for bacterial keratitis, showing comparable efficacy to fortified antibiotic solutions with fewer side effects .

Respiratory Tract Infections

A multicenter surveillance trial demonstrated that this compound had a potential empiric use rate of 90.6% for respiratory tract infections, outperforming other antibiotics like ciprthis compound and ampicillin . The study involved 6,967 clinical isolates, confirming this compound's broad spectrum of activity.

Urinary Tract Infections

In clinical evaluations, this compound showed a high success rate in treating urinary tract infections, with low resistance rates reported (0.5% among tested isolates) . The drug's excellent oral bioavailability (approximately 98%) allows for effective outpatient treatment regimens .

Ocular Infections

In a study comparing this compound to fortified cefazolin and tobramycin for bacterial keratitis, healing rates were similar between groups at 28 days (89% for this compound vs. 86% for fortified antibiotics). Patients using this compound reported significantly less discomfort upon instillation .

Resistance Patterns

While this compound is generally effective, there are concerns regarding the emergence of bacterial resistance. Resistance mechanisms include mutations in DNA gyrase and plasmid-mediated resistance factors. Continuous monitoring of resistance patterns is essential as fluoroquinolone usage increases .

Pharmacokinetics

• Absorption : After oral administration, peak serum concentrations are reached within one to two hours.
• Distribution : this compound penetrates various tissues, including lung tissue and prostatic fluid.
• Metabolism : It undergoes minimal metabolism, with 65% to 80% excreted unchanged via the kidneys within 48 hours .

Data Summary Table

氧氟沙星通过抑制细菌 DNA 旋转酶和拓扑异构酶 IV 的活性发挥其抗菌作用。这些酶对于细菌 DNA 的超螺旋和解螺旋至关重要，这些过程对于 DNA 复制和转录是必要的。 通过抑制这些酶，氧氟沙星阻止细菌复制和修复其 DNA，导致细菌细胞死亡 .

类似化合物： 与氧氟沙星类似的化合物包括其他氟喹诺酮类，如左氧氟沙星、环丙沙星和莫西沙星。 这些化合物具有类似的作用机制，但在活性谱和药代动力学特性方面有所不同 .

氧氟沙星的独特性： 氧氟沙星在对抗革兰氏阳性菌和革兰氏阴性菌方面具有平衡的活性。与其他一些氟喹诺酮类相比，它还以副作用发生率相对较低而闻名。 此外，氧氟沙星已被广泛研究，并在科学文献中有很好的记录，使其成为研究和临床应用的宝贵化合物 .

Ofloxacin is a fluoroquinolone antibiotic known for its broad-spectrum antibacterial activity. It is primarily used to treat infections caused by both Gram-positive and Gram-negative bacteria. This article explores the biological activity of this compound, focusing on its mechanisms of action, pharmacokinetics, and clinical efficacy based on diverse research findings.

This compound exerts its bactericidal effects by inhibiting bacterial DNA replication. It achieves this by binding to two key enzymes: DNA gyrase and topoisomerase IV . These enzymes are crucial for managing DNA supercoiling during replication and transcription. The binding affinity of this compound for bacterial DNA gyrase is approximately 100 times greater than for mammalian topoisomerase, which contributes to its selective toxicity against bacteria .

Pharmacodynamics

• Bactericidal Activity : this compound demonstrates significant in vitro activity against various bacterial strains, particularly Enterobacteriaceae. Research indicates that it is more potent than other quinolones, such as norfloxacin, against Acinetobacter spp. and Staphylococcus spp. .
• Minimum Inhibitory Concentration (MIC) : Studies show that most strains of Pseudomonas aeruginosa are inhibited at concentrations below 2 mg/l , highlighting its effectiveness against resistant strains .

Pharmacokinetics

• Bioavailability : this compound has a high bioavailability of approximately 98% when administered orally .
• Protein Binding : The drug binds to plasma proteins at about 32% , influencing its distribution and elimination .
• Elimination : this compound is primarily excreted through the kidneys, with 65% to 80% of an oral dose eliminated unchanged in urine within 48 hours .

Case Studies and Research Findings

• In Vivo Studies : In comparative studies, this compound exhibited up to five times greater in vivo antibacterial activity than pefloxacin and norfloxacin. This enhanced efficacy is attributed to favorable pharmacokinetics and bacterial susceptibility profiles .
• Time-Kill Studies : A study measuring the bactericidal activity of this compound found that it had a mean time to kill of approximately 33.1 minutes , with a prolonged post-antibiotic effect (PAE) lasting around 157.7 minutes after exposure . This contrasts sharply with ceftriaxone, which showed significantly slower bactericidal activity.
• Resistance Patterns : this compound has been shown to maintain efficacy against strains with intermediate susceptibility, particularly in infections caused by Salmonella Typhi, indicating its potential utility in treating resistant infections when appropriate dosing is maintained .

Comparative Activity Against Other Antibiotics

Basic Research Questions

Q. How to formulate a research question on ofloxacin's mechanisms of bacterial resistance?

• Methodology : Use frameworks like PICO (Population, Intervention, Comparison, Outcome) to structure the question. For example:

• Population: Bacterial strains with reduced this compound susceptibility.
• Intervention: Genetic or phenotypic analysis of resistance mechanisms (e.g., mutations in gyrase genes).
• Comparison: Susceptible vs. resistant strains.
• Outcome: Identification of resistance markers or efflux pump activity.
  • Key Consideration : Ground the question in literature gaps, such as understudied resistance pathways in Gram-negative bacteria .

Q. What methodologies are critical for designing pharmacokinetic (PK) studies of this compound in pediatric populations?

• Methodology :

• Use population PK modeling to account for age-related variables (e.g., renal maturation, body weight).
• Incorporate sparse sampling to minimize ethical concerns in children.
• Validate assays (e.g., HPLC) for plasma concentration measurement.
  • Data Consideration : A study found lower drug exposures in children vs. adults, highlighting the need for adjusted dosing regimens .

Q. How to integrate existing literature into experimental design for this compound studies?

• Methodology :

• Conduct systematic reviews to identify gaps (e.g., limited data on biofilm penetration).
• Reference protocols from authoritative sources (e.g., WHO reports on MDR-TB treatment) for reproducibility.
• Use tools like PRISMA for transparent literature synthesis .

Advanced Research Questions

Q. How does this compound's efficacy compare to later-generation fluoroquinolones in MDR-TB treatment?

• Methodology :

• Conduct individual patient data (IPD) meta-analyses of observational cohorts.
• Adjust for confounders (e.g., resistance profiles, comorbidities) using multivariate regression.
  • Key Findings :

• Later-generation FLQs showed superior treatment success, particularly in this compound-resistant isolates .

Q. How to evaluate this compound's bactericidal activity in complex infection models (e.g., osteo-articular infections)?

• Methodology :

• Use in vitro models with infected eukaryotic cells (e.g., osteoblasts) to simulate host-microbe interactions.
• Measure log10 CFU reductions across antibiotic concentrations.
  • Example Data :

• Dose-response analysis confirmed significant bactericidal effects at maximal concentrations .

Q. How to resolve contradictions between observational studies and RCTs on this compound efficacy?

• Methodology :

• Apply GRADE criteria to assess evidence quality (e.g., risk of bias in observational data).
• Use sensitivity analyses to test robustness of meta-analysis conclusions.
  • Case Study : IPD meta-analyses reconciled heterogeneity across 32 cohorts by standardizing outcome definitions (e.g., "treatment success") .

Q. Methodological Best Practices

Q. How to ensure transparency and reproducibility in this compound research?

• Guidelines :

• Deposit raw data (e.g., MIC values, PK curves) in public repositories like Zenodo.
• Follow journal standards for experimental details (e.g., NCCLS protocols for antimicrobial susceptibility testing) .

Q. What statistical approaches are optimal for analyzing this compound dose-response relationships?

• Recommendations :

• Use nonlinear mixed-effects modeling (NONMEM) for PK/PD integration.
• Apply ANOVA with post-hoc tests (e.g., Tukey’s) for multi-concentration experiments .