INTRODUCTION:

This study was carried out to assess the safety and effectiveness of using the new generation fluoroquinolone garenoxacin as an empirical treatment for infected wounds in the management of skin and skin structure infections (SSSI). Garenoxacin inhibits DNA transcription and replication by acting on DNA gyrase and DNA topoisomerase IV, just like other fluoroquinolones.¹Trauma, which can be chosen or unintentional, is the most frequent underlying cause of all wounds. In particular populations, such as diabetics or the elderly, wounds are more likely to develop complications or to become super-infected. Only the skin and superficial soft tissue may be affected at first, but as the infection worsens, fascia, muscle, joints, and bone are likely to be affected as well. Carefully evaluating wound care procedures, such as cleansing and debridement, dressing, and choosing the best empirical antibiotic medication, is necessary to treat these infections successfully.²

Surgical wound infections are less common when antibiotic prophylaxis is appropriately delivered, which is advised for all clean-contaminated, contaminated, and unclean surgeries.³ The physical disruption of the skin, which serves as the screening barrier for pathogen infections in the internal tissues, results in a wound. Infection is the outcome of germs piercing this barrier.^4,5 A novel quinolone antibiotic called garenoxacin was created in Japan. One distinctive feature of the novel quinolone garenoxacin is the absence of a fluorine molecule at the C-6 position. Garenoxacin is highly effective against a wide range of bacterial illnesses.⁶

According to the National Comprehensive Cancer Network's (NCCN) and the Infectious Diseases Society of America's (IDSA) current practice guidelines, B-I and category 2A prophylaxis, respectively, are advised for limited patients receiving chemotherapy whose expected neutrophil count is less than 0.1109/l for more than seven days. Therefore, the best patient features, when to start, and whether to take antibiotics as preventative measures have not yet been determined. Only Japan has authorised the new des-F (6)-quinolone garenoxacin. It is mostly eliminated in bile and has effectiveness against a broader variety of pathogens, including types that are resistant to conventional quinolones. ^{7, 8, 9.}

When choosing antibacterial treatments for patients, drug susceptibility offers valuable information. Nevertheless, the selection of antimicrobial drugs must take into account both penetration into the infection site and the minimum inhibitory concentration (MIC) value.¹⁰

1-Cyclopropyl-8- (difluoromethoxy) Garenoxacin [(1R)-1-methyl-2, 3-dihydro-1H-isoindol -5- yl] -7- A quinolone antibiotic, 4-oxo-1, 4-dihydroquinoline-3-carboxylic acid, has a wide spectrum of antibacterial action against both Gram-positive and Gram-negative bacteria, including some strains that are resistant to quinolones.^[11] Numerous techniques have been developed to determine if biological samples contain Garenoxacin alone or in combination with other drugs. Among them is RP-HPLC.¹²

MECHANISM OF ACTION:

Inhibition of DNA Gyrase (Topoisomerase II):

The introduction of negative supercoils into DNA-by-DNA gyrase is essential for reducing torsional strain during transcription and replication.
Garenoxacin causes double-strand breaks and bacterial cell death by attaching itself to the A subunit of DNA gyrase and blocking the re-ligation of the cleaved DNA strands.¹³

Inhibition of Topoisomerase IV:

During cell division, topoisomerase IV plays a role in the decatenation (separation) of replicated DNA strands.

By blocking this enzyme, appropriate chromosome segregation is disrupted, which inhibits bacterial growth

and causes cell death.¹⁴

PHYSICAL AND CHEMICAL PROPERTY:

Table .no 1 Physical and chemical property Garenoxacin

Chemical Name	1-Cyclopropyl-8-(difluoromethoxy)-7-[(1R)-1-methyl- 2,3dihydro-1H-isoindol-5-yl]-4-oxo-1,4-oxy-1,4- dihydroquinoline-3-carboxylicacidmonomethanesulfonate
CAS Number	194804-75-6
Molecular Formula	C₂₃H₂₀F₂N₂O₄CH₄O₃S
Molecular Weight	522.52g/mol
Half Life	20 hours
Solubility	Insoluble in water, sparingly soluble in methanol, very soluble in Acetronitrile DMSO
Category	Antibiotic
BCS	Class II

Fig. 1: Chemical structure of Garenoxacin

Pharmacokinetics of Garenoxacin:

A new des-F (6) quinolone antibiotic, garenoxacin exhibits a wide range of efficacy against both Gram-positive and Gram-negative bacteria, including those that are resistant to multiple drugs. To maximise its therapeutic utility, its pharmacokinetic characteristics have been thoroughly investigated.

· Oral Bioavailability: Garenoxacin is quickly absorbed when taken orally, reaching peak plasma concentrations one to two hours after the dose.

· Proteoprotein Binding: At different doses, over 75% of garenoxacin binds to plasma proteins.^[15]

· Hepatic Metabolism: Glucuronidation and other phase II processes are the main ways that garenoxacin is metabolised in the liver.

· Cytochrome P450 Interaction: A lower risk of drug-drug interactions is suggested by minimal engagement with the cytochrome P450 enzyme system.^[16]

Pharmacodynamics of Garenoxacin:

Pharmacodynamic Parameters: The area under the concentration-time curve divided by the lowest inhibitory concentration (AUC/MIC) is the best indicator of garenoxacin's effectiveness. Research utilising neutropenic murine thigh infection models has shown that improved bacterial eradication is predicted by greater AUC/MIC ratios.¹⁷

Analytical Method Development:

The process of developing an accurate assay to ascertain the composition of formulations is known as analytical technique development. Developing an analytical approach entails determining whether it is appropriate for use in a laboratory. Analytical methods must adhere to GMP and GLP procedures and fulfil ICH guidelines' approval requirements. Q2 (R1).¹⁸

High Performance Liquid Chromatography (HPLC): Originally called high-pressure liquid chromatography, HPLC is a technique used in analytical chemistry to separate, identify, and quantify specific components in mixtures. Among other things, the mixtures may originate from liquid solutions that have been dissolved from biological, environmental, medicinal, chemical, or dietary sources.¹⁹

Ultra-high performance liquid chromatography (UHPLC):

Particles smaller than the 2.5–5 μm ones commonly employed in high-performance liquid chromatography (HPLC) can be held in columns used in ultra-high-performance liquid chromatography (UHPLC). The fundamental premise of UHPLC, which operates under the same assumptions as HPLC, is that efficiency and, consequently, resolution accretion increase as column packing particle size decreases. Smaller particle separations in columns result in increased efficiency per unit of time; however, efficiency cannot be reduced by higher mobile phase flow rates or linear velocities. Following characteristics, It is possible to achieve unprecedented levels of peak resolution and delicate particle speed. It is well known according to van Deemter equations that the effectiveness of the chromatographic process is directly correlated with the reduction in particle size. His model-characterized band broadening demonstrates that the relationship between the height equivalent of a theoretical plate (HETP) and linear velocity depends on the size of the particles packed into the analytical column.²⁰

Reverse phase high performance liquid chromatography (RP-HPLC):

A polar mobile phase and a non-polar stationary phase are used in reversed-phase liquid chromatography (RP-LC), a kind of liquid chromatography, to separate organic molecules.^21,22,23The vast majority of separations and analyses carried out with high-performance liquid chromatography (HPLC) in recent years have been carried out in the reversed phase mode. The components of the sample are kept in the system in reversed phase mode to a greater extent if they are hydrophobic.^[24]

Validation:

Validation of the analytical method is a necessary prerequisite for carrying out the chemical evaluation. Method validation is a process used in various evaluations to confirm that an analytical test system is appropriate for its intended use and able to produce useful and authentic analytical data. A validation examine includes testing multiple attributes of a method to determine that it may provide useful and valid facts whilst used robotically. The validation test should incorporate standard test circumstances, including product excipients, in order to precisely examine method parameters. As a result, a method validation analysis is unique to each product.²⁵

METHOD VALIDATION Ø

Accuracy

Precision

Linearity

Specificity

Ruggedness

Robustness

Limit Of Detection

Limit

Reported method for Garenoxacin

Unlike conventional quinolones, garenoxacin is a special fluoroquinolone that does not contain the fluorine atom at position C6, which was previously believed to be crucial. Garenoxacin, owing to unique substitutions at the 6th, 7th, and 8th position in quinolone ring essays lower MIC90 and higher AUC/MIC90 ratio governing higher potency, killing power, lower susceptibility to efflux, and resistance mechanisms against prevailing respiratory Gram-positive/harmful and atypical pathogens, including Streptococcus pneumoniae compared to other fluoroquinolones.^26,27

Natsumi Hara. In 2023, she and her coworkers released the results of their investigation. A Case Report and Literature Review on Garenoxacin-Induced Fixed Drug Eruption.

Overview: paper provides a case study of a 25-year-old woman who had several fixed drug eruptions (FDE).

Case Presentation:

Garenoxacin is a representative causative medication that causes a fixed drug eruption. To clarify the features of garenoxacin-related drug eruption, we evaluated all English and Japanese reported instances of drug eruption induced by garenoxacin. Garenoxacin has previously caused skin responses, which showed it was the perpetrator. A study of past cases revealed 11 occurrences of garenoxacin-induced drug eruptions, with multiple FDE being the most common form. Garenoxacin is a known cause of FDE, however it is underreported in English-language literature. A review of eleven cases (including this one) revealed: The most common reaction is multiple fixed drug eruption (8 instances). Other responses include maculopapular rash (2 cases) and drug-induced hypersensitivity syndrome (1 case). Diagnostic procedures include oral challenge tests (most accurate), patch testing (positive in 57% of instances), and lymphocyte stimulation tests (usually negative).²⁸

Yoko Matsuda. In 2017, he and her coworkers released the results of their investigation. The purpose of the case report named "A Case of Macrolide-Refractory Mycoplasma pneumoniae" Pneumonia in pregnancy. Treated with Garenoxaci

Overview: A 40-year-old lady, 13 weeks pregnant with twins, appeared with a cough and fever and was diagnosed with pneumonia.

The introduction and background sections provide context, history, or background information to set the stage for the conversation.

The main content focuses on major ideas, concerns, or arguments. Specific topics covered include [name main arguments, facts, or sections].

Analysis and Discussion - The paper employs comparisons, evaluations, case studies, or expert opinions to support its findings.

The conclusion and recommendations section outlines significant insights and offers suggestions for future steps or consequences.²⁹

Mushino T. In 2017, he and her coworkers released the results of their investigation. An Optimal Approach to Fluoroquinolone Garenoxacin Prophylaxis in Patients with Hematological Malignancies and Chemotherapy-Induced Neutropenia.

Core Topic Analysis Discusses the major topic in depth, highlighting its importance and relevance. To help grasp the topic, historical or contextual background is provided.

Data and Evidence. Include statistical data, case studies, or real-world examples to back up essential ideas. Uses comparisons and patterns to demonstrate the findings.

Challenges and Issues Identifies significant obstacles linked with the topic. Assesses potential risks and hurdles to success.

Solutions and Recommendations Suggests actionable methods to address the challenges raised.

Policy proposals, best practices, and industry insights may all be included.

Conclusion and Final Thoughts Summarizes key findings from the document. Provides final recommendations or calls to action.³⁰

Yuka Yamagishi. In 2017, he and her coworkers released the results of their investigation. The article "Proposed Pharmacokinetic-Pharmacodynamic Breakpoint of Garenoxacin and Other Quinolones" analyzes the significance, obstacles, and potential solutions for the main issue. These breakpoints help predict the effectiveness of antibiotics against key respiratory pathogens: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, which are major causes of community-acquired pneumonia (CAP).

Methods: - The MCS used plasma concentration data from healthy subjects and MIC distributions from clinical isolates collected in Japan (2009 and 2012).

GRNX’s PK-PD breakpoints (0.5 µg/mL for S. pneumoniae and 0.125 µg/mL for H. influenzae and M. catarrhalis) indicate superior efficacy compared to LVFX, MFLX, and STFX against CAP pathogens. The study suggests GRNX as a valuable treatment option for respiratory infections in Japan, where its breakpoint had not been previously established by organizations like CLSI, EUCAST, or JSC.

- Target fAUC/MIC values were set at ≥ 30 for S. pneumoniae and ≥ 100 for Gram-negative bacteria.^[31]

Yoshio Kawakami. A case of anaphylaxis In 2017, Kawakami et al. reported a rare case of anaphylaxis caused by the quinolone antibiotic, Garenoxacin Mesylate Hydrate (GRN). A 64-year-old lady developed anaphylaxis 2.5 hours after using GRN (400 mg) with other drugs (montelukast, carbocisteine) to treat an upper respiratory tract infection. Symptoms began with pruritis on her face and hands after washing, which progressed to generalized erythema and wheals. and wheezing upon arriving at the emergency room.

She was successfully treated with methylprednisolone sodium succinate, chlorpheniramine maleate, salbutamol sulfate, and oxygen, and her symptoms improved. Four weeks later, prick tests revealed a positive reaction to GRN (confirmed with 1% and 2% solutions), but tests for the other medications, pickled scallops (taken during dinner), and a moisturizer came back negative. Oral challenge testing with all medications except GRN yielded negative results. Prick tests with other quinolones (levofloxacin and ciprofloxacin) yielded marginally positive findings, indicating potential cross-sensitivity; nevertheless, a basophil activation test (BAT) for GRN was negative. This is the first detailed report of GRN-related anaphylaxis, despite the fact that 21 prior occurrences have been identified in Japanese pharmaceutical data since 2008.
The delayed start of symptoms (2.5 hours) may be due to GRN's pharmacokinetics (tmax of 2.46 hours), which could be aggravated by bathing-induced temperature increase.³²

Rajendra B. Kakde in 2017, he and his coworkers released the study's findings. Solid Phase Extraction-HPLC Method for Determination and Pharmacokinetic Study of Garenoxacin in Rat Plasma Following Oral Administration. It describes the development and validation of a bioanalytical method for quantifying Garenoxacin, a quinolone antibiotic, in rat plasma using solid phase extraction (SPE) and high-performance liquid chromatography with photodiode array detection (HPLC-PDA), as well as its application to a pharmacokinetic study in rats. The method used a thermo-bds hypersil C18 column with an isocratic mobile phase of acetonitrile and 25 mM potassium dihydrogen phosphate (pH 3.3) at a 25:75 ratio, with detection at 279 nm. Ciprofloxacin served as the internal standard. The assay was linear across a concentration.

The assay has a linear concentration range of 15-44 µg/ml and an LLOQ of 15 µg/ml. Extraction recoveries above 77%, accuracies remained within 3.97%, and intra- and inter-day precisions were less than 9.36%. The approach was evaluated for specificity, linearity, precision, accuracy, recovery, and stability under a variety of conditions (for example, freeze-thaw cycles and long-term storage at -80°C for 20 days), demonstrating its dependability and reproducibility. The study finds that the SPE-HPLC-PDA approach is simple, fast, sensitive, and accurate for Garenoxacin analysis in biological samples, making it a useful tool for pharmacokinetic studies.

This study created and validated a bioanalytical method for quantifying Garenoxacin, a quinolone antibiotic, in rat plasma after oral treatment. The approach used solid phase extraction (SPE) in conjunction with high-performance liquid chromatography (HPLC) and photodiode array (PDA). The method used a thermo-bds hypersil C18 column with an isocratic mobile phase of acetonitrile and 25 mM potassium dihydrogen phosphate (pH 3.3) at a 25:75 ratio, with detection at 279 nm. Ciprofloxacin served as the internal standard. The test has a linear concentration range of 15-44 µg/ml, with a lower limit of quantification (LLOQ) of 15 µg/mL. Extraction recoveries exceeded 77%, accuracy was within 3.97%, and intra- and inter-day precisions were less than 9.36%, meeting bioanalytical requirements.³³

In January 2016, Pravati Dutta et al. published "Clinical Utility of Garenoxacin in Lower Respiratory Tract Infections: A Retrospective Analyzes." It assesses the efficacy and safety of Garenoxacin, a des-fluoroquinolone antibiotic, in treating lower respiratory tract infections (LRTIs) in the community, particularly in cases complicated by comorbidities, antibiotic resistance, and failure of first-line therapy. Pravati Dutta et al. published a study in January 2016 called "Clinical Utility of Garenoxacin in Lower Respiratory Tract Infections: A Retrospective Analyzes." It assesses the efficacy and safety of Garenoxacin, a des-fluoroquinolone antibiotic, in treating lower respiratory tract infections (LRTIs) in the community, particularly in cases complicated by comorbidities, antibiotic resistance, and failure of first-line therapy. Results indicate a 100% clinical success rate, with 96% success by day 5 and no reported treatment failures or substantial side events necessitating withdrawal. The average treatment time for acute bronchitis was 7.9 days, while AECOPD was 7.1 days. Laboratory results from 47% of patients showed increased leukocyte and neutrophil counts by day 5.

The topic emphasizes the global burden of LRTIs, particularly AECOPD, and the growing issue antibiotic resistance, including penicillin-resistant S. pneumoniae (PRSP) and quinolone-resistant strains (QRSP). Garenoxacin's unusual structure, lacking the C6 fluorine atom typical of fluoroquinolones, provides a lower MIC₉₀ and higher AUC/MIC₉₀ ratio, boosting effectiveness against resistant infections like PRSP and QRSP compared to moxifloxacin and levofloxacin. Previous studies have shown that Garenoxacin has an efficacy range of 89-96% in AECOPD and LRTI, with superior in vitro action against multidrug-resistant S. pneumoniae. The study's findings support this, indicating Garenoxacin as a beneficial alternative, particularly in complex cases with comorbidities or prior treatment failure.³⁴

In 2016, A. P. Edlabadkar and A. P. Rajput published an article in Der Pharmacia Lettre on "Development of Four Simple UV-Spectrophotometry Methods for Estimation of Garenoxacin Mesylate in Bulk Material and Pharmaceutical Formulation." It details the development and validation of four UV-spectrophotometric methods for quantifying Garenoxacin Mesylate (GRN), a quinolone antibiotic used to treat respiratory and urinary tract infections, in bulk and tablet forms, using distilled water as a solvent. GRN stock solutions were created using distilled

water, and calibration curves with outstanding linearity (r2 > 0.997) were created throughout a concentration range of 3–18 µg/mL. When GRN in tablets (200 mg label claim) was evaluated using these methods, the results showed great accuracy, ranging from 98.15% to 99.39% of the claimed amount.Validation in compliance with ICH standards Precision (intra- and inter-day %RSD < 2), repeatability (%RSD < 2), ruggedness (%RSD < 2 across analysts), linearity, accuracy (recovery 98.04-100.17%), and sensitivity (LOD 0.04-0.11 µg/mL, LOQ 0.14-0.35 µg/mL). The study highlights the reliability, affordability, and ease of use of these processes, which employ distilled water as a solvent instead of more complex systems like those utilized in previously reported methods (e.g., gRP-HPLC). There were no prior UV spectrophotometric methods employing distilled water for GRN quantification in the literature, so this is a novel addition. According to the authors, these methods are suitable for regular GRN analysis in pharmaceutical formulations and bulkmaterials.³⁵

The study was published in 2021 by Ajitha Azhakesan A and her colleagues. ln order to develop and validate a novel stability-indicating method based on QbD for the assay and dissolution of garenoxacin in tablets. It describes how a Quality by Design (QbD) methodology was used to create and validate a novel stability-indicating method for the assay and dissolving of garenoxacin in 200 mg garenoxacin tablets. The des-fluoro (6) quinolone antibiotic garenoxacin mesylate, which is sold under the brand name Geninax in Japan, has a broad-spectrum effect on antimicrobial resistance. With peak purity verified under stressful circumstances, the RP-HPLC test technique was linear, robust, accurate (99.8–100.5% recovery), and exact (RSD ≤ 0.48%). Variations in API particle size had no effect on the dissolving method's consistent drug release (Q ≥ 80% at30min).

The particle size analysis was dependable; D90 values of 220 µm and 92 µm indicated little impact from dissolution. Stability-Indicating Assay Method: A reverse-phase high-performance liquid chromatography (RP-HPLC) method was created with a 0.1% formic acid mobile phase in water and methanol (70:30 v/v) and a photodiode array (PDA) detector to detect at 280 nm and determine peak purity. dissolving Test Method: Using USP Apparatus II (paddle) and 0.1 N hydrochloric acid (900 mL) at 50 rpm and 37 ± 0.5°C, a dissolving method was developed with a 30-minute endpoint (Q ≥ 80% drug release). With UV detection at 280 nm, validation verified linearity (2.9–34.2 µg/mL), specificity, accuracy, precision, solution stability, and filter compatibility.

Particle Size Measurement: Using the Malvern Mastersizer 2000 (wet dispersion with liquid paraffin), a novel technique for determining the particle size of garenoxacin mesylate API was created and verified for accuracy, intermediate accuracy, and robustness (RSD < 10%).

The dissolving profile was not significantly affected by the particle sizes (D90: 92 µm and 220 µm). BCS Solubility Study: Using a modified shake flask method, the solubility of garenoxacin mesylate API was evaluated spanning pH 1–4.5. The results confirmed high solubility (less than 250 mL was needed to dissolve 200 mg), validating sink conditions for dissolution testing.³⁶

The paper was published in 2019 by Ajitha A. and her colleagues. In order to establish a bioanalytical approach to validate the presence of garenoxacin mesylate in human plasma using RP-HPLC

Development of Methods:

Conditions for Chromatography: With a mobile phase consisting of 0.1% orthophosphoric acid and acetonitrile (50:50 v/v), a flow rate of 1.0 mL/min, detection at 240 nm, an injection volume of 50 µL, and a column temperature of 30°C, separation was accomplished on a Zorbax Eclipse XDB C18 column (250 × 4.6 mm, 5 µm).

Sample Preparation: Plasma samples (250 µL) were spiked with garenoxacin mesylate (0.04–4 µg/mL) and internal standard (50 µL, 4 µg/mL), extracted with acetonitrile, and centrifuged to obtain a clear supernatant for analysis.

Retention Times: Garenoxacin mesylate eluted at 4.0 minutes, and ciprofloxacin hydrochloride at 3.4 minutes. Validation (per ICH Q2B guidelines): System Suitability: Six injections of a medium QC sample showed consistent retention times and peak areas (%CV ≤ 0.17).

Selectivity/Specificity: No interference from endogenous plasma components was observed at the analyte and internal standard retention times.

The lower limit of quantification (LLOQ) is 0.04 µg/mL (S/N ratio = 21), and the linearity is linear over 0.04–4 µg/mL (R2 = 0.999).

Precision and Accuracy: Accuracy ranged from 97.30% to 102.77%, while intraday and interday precision (%CV) varied from 1.82% to 7.77% and 3.47% to 6.63%, respectively.

Recovery: The internal standard had a mean recovery of 97.86%, while garenoxacin had mean recoveries of 99.72% (LQC), 98.13% (MQC), and 99.07% (HQC).

*Stability*: Stable in plasma at -28°C and -80°C for 60 days (97.42–100.93%) and in stock solution for 9 hours at room temperature (98.04–101.75%) ^[37]

The paper was published in 2019 by Aboli Edlabadkar and her colleagues. For the purpose of optimizing, developing, and validating garenoxacin mesylate in bulk and tablets using the RP-HPLC method, a QBD approach. creation, refinement, and verification of a reverse-phase high-performance liquid chromatography (RP-HPLC) technique employing Analytical Quality by Design (AQbD) for the analysis of garenoxacin mesylate (GRN) in tablet and bulk form. The quinolone antibacterial drug garenoxacin mesylate is used to treat a variety of bacterial diseases, such as urinary tract and respiratory infections.

Method Development and Optimization

Chromatographic Conditions: With a mobile phase of acetonitrile: water (60:40 v/v, pH 3.5 adjusted with 0.1% orthophosphoric acid), a flow rate of 1.0 mL/min, detection at 280 nm using a PDA detector, and an injection volume of 20 µL, the analysis was carried out on a PrincetonSPHERE ULTIMA C18 column (250 × 4.6 mm, 5 µm). The AQBD Method: Critical method parameters (CMPs) were screened using a seven-factor, eight-run Taguchi design, which revealed that pH, flow rate, and mobile phase ratio were important variables. These parameters were tuned during 20 experimental runs using a central composite design (CCD) with α=1, focusing on the critical analytical attributes (CAAs) of theoretical plates (TP), retention time (Rt), and tailing factor (TF). Statistical Analysis: Data was analyzed using a second-order polynomial model utilizing Design Expert software (v8.0.4.1), and ANOVA verified the model's significance (p-values < 0.0085).

Validation (per ICH Q2(R1) guidelines):

System Suitability: Rt = 5.15 min, TP = 2257, TF = 1.045, and %RSD were all within acceptable bounds in six replicates at 10 µg/mL.

Linearity: Using the equation y = 28578x + 12176, linear over 2–12 µg/mL (R2 = 0.998).

Precision: At 4, 6, and 8 µg/mL, the intra-day precision (%RSD 0.36–0.85) and inter-day precision (%RSD 0.37–1.20) were less than 2%.

80%, 100%, and 120% recovery rates ranged from 99 to 101% (%RSD 0.71–1.23), indicating accuracy. ³⁸

CONCLUSION:

Garenoxacin, a unique des-fluoroquinolone antibiotic, demonstrates promising broad-spectrum activity against various Gram-positive and Gram-negative bacteria, including resistant strains. Its mechanism of action, involving dual inhibition of DNA gyrase and topoisomerase IV, provides it with enhanced bactericidal potential. The pharmacokinetic and pharmacodynamic profiles of garenoxacin support its efficacy and safety in treating a range of infections, particularly skin, soft tissue, and respiratory tract infections. Analytical methods such as RP-HPLC, UHPLC, and UV-spectrophotometry have been successfully developed and validated for its quantification, adhering to ICH and QbD guidelines. Clinical studies and case reports affirm its therapeutic effectiveness, although adverse effects like fixed drug eruptions and rare cases of anaphylaxis must be monitored. Overall, garenoxacin stands out as a valuable addition to the fluoroquinolone class, offering a potent alternative in the face of rising antimicrobial resistance.

REFERENCES

1. Ince D, Zhang X, Silver LC, Hooper DC. Dual targeting of DNA gyrase and topoisomerase IV: target interactions of garenoxacin (BMS-284756, T-3811ME), a new desfluoroquinolone. Antimicrob Agents Chemother. 2002; 46(11): 3370-80.

2. Lipsky BA. Evidence-based antibiotic therapy of diabetic foot infections. FEMS Immunol Med Microbiol.

3. Woods RK, Dellinger EP. Current guidelines for antibiotic prophylaxis of surgical wounds. Am Fam Physician. 1998; 57(11): 2731-40.

4. Bisno AL, Stevens DL. Streptococcal infections of skin and soft tissues. N Engl J Med. 1996; 334(4): 240-5.

5. Janda JM, Abbott SL, Brenden RA. Overview of the etiology of wound infections with particular emphasis on community-acquired illnesses. Eur J Clin Microbiol Infect Dis. 1997; 16(3): 189-201.

6. Liebetrau A, Rodloff AC, Behra-Miellet J, Dubreuil L: In vitro activities of a new des-fluoro (6) quinolone, garenoxacin, against clinical anaerobic bacteria. Antimicrob Agents Chemother. 2003, 47: 3667-71.10.1128/AAC.47.11.3667-3671.2003

7. Takahata M, Mitsuyama J, Yamashiro Y, Yonezawa M, Araki H, et al. In vitro and in vivo antimicrobial activities of T-3811ME, a novel des-F(6)-quinolone. Antimicrob Agents Chemother. 1999; 43: 1077-1084.

8. Fung-Tomc JC, Minassian B, Kolek B, Huczko E, Aleksunes L, et al. (2000) Antibacterial spectrum of a novel des-fluoro (6) quinolone, BMS-284756.Antimicrob Agents Chemother 44: 3351-3356.

9. Nord CE, Gajjar DA, Grasela DM. Ecological impact of the des-F (6)-quinolone, BMS-284756, on the normal intestinal microflora. Clin Microbiol Infect. 2002; 8: 229-239.

10. Ishii Y. Antibiotic susceptibility testing and breakpoint. –Their problems and future prospects– JPN J Chemother. 2011; 59:454–59. Japanese.

11. Anon, Schering-Plough Reports Garenoxacin NDA Accepted for FDA Review. Available at: http://www.drugs.com/nda/garenoxacin_060213.html [Accessed December 10, 2015].

12. A. Unnisa, S.S. Ali and K.S.C., World J. Pharm. Pharmaceut. Sci. 2014; 3: 1767.

13. Jones RN, Fritsche TR, Sader HS, et al. Garenoxacin (BMS-284756): In Vitro Antimicrobial Spectrum, Mechanisms of Action, and Resistance Development. Clinical Infectious Diseases. 2005; 41(Suppl 2): S87–S98.

14. Hooper DC. Mechanisms of Action of Antimicrobial Agents. Principles and Practice of Infectious Diseases, 8th ed. Elsevier, 2015.

15. D. A. Gajjar, A. Bello, Z. Ge, L. Christopher, and D. M. Grasela, Multiple-Dose Safety and Pharmacokinetics of Oral Garenoxacin in Healthy Subjects, DOI: 10.1128/AAC.47.7.2256–2263.2003 Vol. 47, No. 7

16. Scott Van Wart, Luann Phillips, Elizabeth A. Ludwig, Rene Russo, Diptee A. Gajjar, Akintunde Bello, Paul G. Ambrose, Christopher Costanzo, Thaddeus H. Grasela, Roger Echols, and Dennis M. Grasela, Population Pharmacokinetics and Pharmacodynamics of Garenoxacin in Patients with Community-Acquired Respiratory Tract Infections, DOI: 10.1128/AAC.48.12.4766–4777.2004, Vol. 48, No. 12

17. D. Andes, W. A. Craig, Pharmacodynamics of the New Des-F(6)-Quinolone Garenoxacin in a Murine Thigh Infection Model. 2003; 47(12). doi.org/10.1128/aac.47.12.3935-3941.2003

18. Chauhan A, Mittu B, Chauhan P. Analytical method development and validation: a concise review. J Anal Bioanal Tech. 2015; 6(1): 1-5.

19. Skoog. D. A, Holler. F. G, Nieman.T.A. Principles of Instrumental Analysis.5th Edition, Thomson Brooks/Cole Asia Pvt. Ltd., Singapore. 2004, 4-7.

20. Willard. H. H, Meritt, L. L, Dean, J. A, Settle. F. A. Instrumental Methods of Analysis. 7th Edition, CBS Publishers and Distributors, New Delhi. 8-10

21. Chatwal. G. R, Anand. S. K. Instrumental Methods of Chemical Analysis. 5th Edition, Himalaya Publishing House, New Delhi. 2007; 2; 624-2.629 5.

22. Sethi. P. D. High Performance Liquid Chromatography. 1st Edition, CBS Publishers and Distributors, New Delhi, 2001, 12-15. 6.

23. Raymond P. W, Principles and Practices of Chromatography, Chrom-Edbook series,2003,1-15 7.

24. Snyder. L. R., Glajch, J. L, Kirkland. J. J. Practical HPLC Method Development. 2 nd Edition, John Wiley & Sons, Inc. A Wiley-interscience Publication, USA.1997: 7-15.

25. Chung C. C, Herman. L, Lee Y.C, Xue-Ming Zang. Analytical Method Validation and Instrument Performance Verification. A John Wiley & Sons, Inc., Publication,2004,11-12

26. Takagi H, Tanaka K, Tsuda H, Kobayashi H Clinical studies of garenoxacin. Int J Antimicrob Agents 2008; 32:468-74.

27. Fung-Tomc JC, Minassian B, Kolek B, Huczko E, Aleksunes L, Stickle T, et al. Antibacterial spectrum of a novel des-fluoro (6) quinolone, BMS- 284756. Antimicrob Agents Chemother. 2000; 44: 3351-6.

28. Natsumi Hara, Natsuko Saito-Sasaki, Yu Sawada Fixed Drug Eruption Caused by Garenoxacin: A Case Report and Literature Review Doi: 10.7759/cureus.48596 2023

29. Yoko Matsuda, Yoshitsugu Chigusa, Eiji Kondoh, Isao Ito, Yusuke Ueda, and Masaki Mandai A Case of Macrolide-Refractory Mycoplasma pneumoniae Pneumonia in Pregnancy Treated with Garenoxacin Volume 2017, Article ID 3520192, 4 pages doi.org/10.1155/2017/3520192

30. Mushino T, Hanaoka N, Murata S, Kuriyama K, Hosoi H, Nishikawa A, Tamura S, Nakakuma H, and Sonoki T, An Optimal Approach for Fluoroquinolone Garenoxacin Prophylaxis in Patients with Hematological Malignancies and Chemotherapy-induced Neutropenia. 2017; 7: 1 DOI: 10.4172/2165-7831.1000161, Volume 7

31. Yuka Yamagishi, Tatsuya Shibata, Satoshi Nakagawa, Nobuhiko Nomura, Junichi Mitsuyama, and Hiroshige Mikamo, Proposed pharmacokinetic–pharmacodynamic breakpoint of garenoxacin and other quinolones, DOI: 10.7883/yoken.JJID.2017.068

32. Yoshio Kawakami, Seiko Mitsui and Kosuke Oka, A Case of Anaphylaxis Following Administration of Garenoxacin Mesylate Hydrate, DOI: 10.4172/2155-9554.1000411. 8(5): 1000411

33. Rajendra B. Kakde, Krutika Warthi, Rahul P. Chilbule, Solid Phase Extraction-HPLC Method for Determination and Pharmacokinetic Study of Garenoxacin in Rat Plasma after Oral Administration. 2017; 10(2): 62-68 http://dx.doi.org/10.20902/IJPTR.2017.1019

34. Pravati Dutta, Shreyas Lathi, K Krishnaprasad, Amit Bhargava, Clinical utility of Garenoxacin in Lower Respiratory Tract Infections: A Retrospective Analyzes: A Case-Cohort Stud, DOI: 10.17354/ijss/2016/02 January 2016 | Vol 3 | Issue 10

35. A. P. Edlabadkar and A. P. Rajput, Development of Four Simple UV-Spectrophotometry Methods for Estimation of Garenoxacin Mesylate in Bulk Material and in Pharmaceutical Formulation, 2016, 8 (11): 213-217

36. Ajitha Azhakesan and Sujatha Kuppusamy, QbD-Based Development and Validation of Novel Stability-Indicating Method for the Assay and Dissolution of Garenoxacin in Garenoxacin Tablets. 2022; 105(2); 78 https://doi.org/10.1093/jaoacint/qsab157

37. Ajitha A, Sujatha K, Abbulu K, Bioanalytical method development and validation of garenoxacin mesylate in human plasma by RP-HPLC. 10(2): 1314-1320

38. Aboli Edlabadkar, Ambarsing Rajput, A QbD Approach- RP-HPLC Method for Optimization, Development and Validation of Garenoxacin Mesylate in Bulk and in Tablets. 2018; 13(4): em26

Received on 10.04.2025 Revised on 12.05.2025

Accepted on 07.06.2025 Published on 12.07.2025

Available online from July 21, 2025

Asian Journal of Pharmaceutical Analysis. 2025; 15(3):213-220.

DOI: 10.52711/2231-5675.2025.00034

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.