Cinoxacin

• CAT Number: I002978
• CAS Number: 28657-80-9
• Molecular Formula: C12H10N2O5
• Molecular Weight: 262.22
• Purity: ≥95%
• Solubility: 10 mM in DMSO
• Storage: -20°C
• IUPAC Name: 1-ethyl-4-oxo-[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid
• InChI: InChI=1S/C12H10N2O5/c1-2-14-7-4-9-8(18-5-19-9)3-6(7)11(15)10(13-14)12(16)17/h3-4H,2,5H2,1H3,(H,16,17)
• InChIKey: VDUWPHTZYNWKRN-UHFFFAOYSA-N
• SMILES: CCN1C2=CC3=C(C=C2C(=O)C(=N1)C(=O)O)OCO3

Cinoxacin (CAT: I002978) is a synthetic antibacterial agent belonging to the fluoroquinolone class of antibiotics. It exhibits broad-spectrum activity against both gram-positive and gram-negative bacteria. Cinoxacin works by inhibiting the action of bacterial DNA gyrase and topoisomerase IV enzymes, which are essential for DNA replication and repair. This inhibition disrupts bacterial DNA synthesis and leads to the bactericidal effect of the drug. Cinoxacin is primarily used in the treatment of urinary tract infections caused by susceptible bacteria. It may also be prescribed for other infections, such as respiratory tract infections and gastrointestinal infections. As with any antibiotic, appropriate use and adherence to dosage guidelines are crucial to ensure effective treatment and minimize the risk of antibiotic resistance.

Reference

[1]. Drug Intell Clin Pharm. 1982 Dec;16(12):916-21. doi: 10.1177/106002808201601203.
Cinoxacin (Cinobac, Eli Lilly & Co.).
Guay DR.
Cinoxacin, a synthetic organic acid antibacterial agent, related structurally to nalidixic and oxolinic acid, has been approved for the treatment of initial and recurrent urinary tract infections (UTIs) caused by susceptible gram-negative microorganisms. The role of cinoxacin in the treatment of UTIs, compared with the usual first-line agents, is uncertain at this time. The efficacy of cinoxacin in the treatment of pyelonephritis, compared with these proven agents, has been examined in only small numbers of patients, and cinoxacin is more expensive than these agents. Cinoxacin may prove valuable in the treatment of prostatitis and in the prophylaxis of recurrent UTIs; further study in these areas is warranted. In the routine treatment of acute UTIs, cinoxacin perhaps should be reserved only for those patients with organisms resistant to usual first-line agents or those who fail to respond to therapy with these agents. In this respect, cinoxacin may, in the future, replace nalidixic acid.
DOI: 10.1177/106002808201601203 PMID: 6759090

[2]. Drugs. 1983 Jun;25(6):544-69. doi: 10.2165/00003495-198325060-00002.
Cinoxacin. A review of its pharmacological properties and therapeutic efficacy in the treatment of urinary tract infections.
Sisca TS, Heel RC, Romankiewicz JA.
Cinoxacin is a urinary antibacterial drug closely related structurally to nalidixic acid. It has a spectrum of in vitro antibacterial activity which qualitatively resembles that of the latter agent, covering most common Gram-negative pathogens, excluding Pseudomonas. In acute or recurrent urinary tract infections it has been shown to be at least as effective as nalidixic acid or co-trimoxazole, and in a few studies was as effective as amoxycillin or nitrofurantoin. Cinoxacin appears to be well tolerated and may have a low propensity to induce bacterial resistance during clinical use, although the latter needs further confirmation. Thus, cinoxacin is an effective alternative for treating urinary tract infections due to common Gram-negative pathogens, and its apparently low incidence of adverse effects may offer worthwhile advantages over the related compounds nalidixic and oxolinic acids. Its use as prophylactic therapy in patients with recurrent urinary tract infections is not yet well established, although this appears a worthwhile area for further study.
DOI: 10.2165/00003495-198325060-00002 PMID: 6347618

[3]. Pharmacotherapy. 1982 Sep-Oct;2(5):266-72. doi: 10.1002/j.1875-9114.1982.tb03195.x.
Cinoxacin: mechanism of action, spectrum of activity, pharmacokinetics, adverse reactions, and therapeutic indications.
Scavone JM, Gleckman RA, Fraser DG.
Cinoxacin, a chemotherapeutic agent that inhibits bacterial DNA synthesis, has recently been approved for the treatment of initial and recurrent bacterial urinary tract infections. Although closely related to nalidixic acid, cinoxacin possesses some distinct characteristics: rapid attainment of therapeutic urinary concentrations and greater activity against strains of Enterobacteriaceae that cause urinary tract infections. Biopharmaceutical properties include serum protein binding of approximately 70%, 50-60% excretion of intact drug in the urine of patients with normal renal function, and an elimination half-life of approximately one hour. The elimination half-life is increased in patients with decreased renal function and when probenecid is coadministered. Adverse events occur infrequently and consist of nausea, vomiting, headache, dizziness, and hypersensitivity reactions. The drug compares favorably with standard therapies for the treatment of bacterial cystitis and recurrent urinary tract infections. Initial studies demonstrate that cinoxacin has substantial efficacy as a prophylactic agent for those women who experience recurrent, symptomatic urinary tract infections.
DOI: 10.1002/j.1875-9114.1982.tb03195.x PMID: 6763208

[4]. J Pharm Sci. 1984 Dec;73(12):1697-700. doi: 10.1002/jps.2600731208.
Time-dependent elimination of cinoxacin in rats.
Koike M, Norikura R, Mizojiri K, Sugeno K.
The effect of the variation of urinary pH on the pharmacokinetics of the acidic antibacterial agent, cinoxacin (pKa 4.60), was examined. Urinary pH of 24-h fasted rats remained at about pH 6 during the daytime, while that of nonfasted rats was high (about pH 7.5) in the morning and gradually decreased to a pH similar to that of the fasted rat in the afternoon. The free fraction of cinoxacin in fasted rat sera in the morning was similar to that in nonfasted rats despite the longer half-life of cinoxacin in fasted rats. In the afternoon the free fraction was slightly different despite similar cinoxacin elimination in fasted and nonfasted rats. These findings seemed to exclude the contribution of protein binding from the causes of increased cinoxacin elimination in nonfasted rats in the morning. Elimination rate constants of cinoxacin obtained with a one-compartment open model correlated well with urinary pH 30 min after injection, suggesting that the urinary pH plays a more important role in cinoxacin elimination. When cinoxacin was orally administered to fasted rats at 11:00, the area under the plasma concentration-time curve was threefold larger than in nonfasted rats. As found with the intravenous administration, this difference may be explained by the prolonged half-life caused by decreased urinary pH after fasting. This study revealed the time-dependent elimination of cinoxacin in nonfasted rats, which is related to physiological change of urinary pH caused by food intake.
DOI: 10.1002/jps.2600731208 PMID: 6527237

[5]. Antimicrob Agents Chemother. 1975 Feb;7(2):159-63. doi: 10.1128/AAC.7.2.159.
Cinoxacin: in vitro antibacterial studies of a new synthetic organic acid.
Lumish RM, Norden CW.
Cinoxacin (compound 64716) is a synthetic organic acid with antibacterial activity against most aerobic gram-negative bacilli. Minimal inhibitory concentrations of cinoxacin (agar-dilution method) were determined for 419 strains. Escherichia coli was the most susceptible group of organisms. The majority of Klebsiella sp., Enterobacter sp., Proteus sp., and Serratia marcescens were inhibited by 8 mug of cinoxacin per ml. Pseudomonas aeruginosa and all gram-positive isolates tested were resistant to 64 mug or less of cinoxacin per ml. Zones of inhibition using a 30-mug disk correlated well with agar-dilution minimal inhibitory concentrations (r = -0.9). Cinoxacin was bactericidal when tested with inocula of 5 x 10(6) organisms per ml. Resistance to cinoxacin was readily developed in all three strains tested by serial passage on drug-containing agar. The in vitro properties of this agent were similar to those of nalidixic acid.
DOI: 10.1128/AAC.7.2.159 PMCID: PMC429096 PMID: 1094949