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Cinoxacin is rapidly absorbed after oral administration. In fluorometric assay, 500-mg dose produced a peak serum concentration of 15 µg/mL, which declined to approximately 1 to 2 µg/mL 6 hours after administration. A 500-mg dose produced an average urine concentration of approximately 300 µg/mL during the first 4 hours and approximately 100 µg/mL during the second 4-hour period. These urine concentrations are many times greater than the minimal inhibitory concentration (MIC) of cinoxacin for most gram-negative organisms commonly found in urinary tract infections.
Ninety-seven percent of a 500-mg oral dose of radiolabeled cinoxacin was recovered in the urine within 24 hours, 60% of which was present as unaltered cinoxacin and the remainder as inactive metabolic products.
The presence of food did not affect the total absorption of cinoxacin. Peak serum concentrations were reduced by 30%, but the 24-hour urinary recovery of antibacterial activity was unaltered. The mean serum half-life is 1.5 hours.
Twenty geriatric patients (ages 70-89, 14 men and 6 women) with creatinine clearance from 58-80 mL/min, were given cinoxacin 500 mg every 12 hours for 7 days. Following the first dose of cinoxacin, the mean peak of the serum concentration was 14 µg/mL. Following the last dose, the mean peak of the serum concentration was 15 µg/mL. The mean urine concentration after 3 hours was 656 µg/mL, at 3-6 hr 1,234 µg/mL, and at 12 hours 33 µg/mL. The mean recovery of unaltered cinoxacin from the urine following the first dose and last dose was 55% and 62%, respectively.
Cinoxacin has in vitro activity against many gramnegative aerobic bacteria, particularly strains of Enterobacteriaceae.Cinoxacin inhibits bacterial deoxyribonucleic acid (DNA) synthesis, is bactericidal, and is active over the entire urinary pH range. Crossresistance with nalidixic acid has been demonstrated.
Conventional chromosomal resistance to cinoxacin taken at recommended doses has been reported to emerge in approximately 4% of patients during treatment; however, bacterial resistance to cinoxacin has not been shown to be transferable via R-factor. Cinoxacin has been shown to be active against most strains of the following organisms both in vitro and in clinical infections (see INDICATIONS):
Diffusion Techniques: Quantitative methods that require measurement of zone diameters give an estimate of bacterial susceptibility. One such procedure is the National Committee for Clinical Laboratory Standards (NCCLS) approved procedure (M2-A5- Performance Standards for Antimicrobial Disk Susceptibility Tests 1993).Â¹ This method has been recommended for use with the 100-µg cinoxacin disk to test susceptibility to cinoxacin.
Interpretation involves correlation of the diameters obtained in the disk test with minimum inhibitory concentrations (MIC) for cinoxacin. Reports from the laboratory giving results of the standard single-disk susceptibility test with a 100-µg cinoxacin disk should be interpreted according to the following criteria (these criteria only apply to isolates from urinary tract infections):
|Zone diameter (mm)||Interpretation|
A report of "susceptible" indicates that the pathogen is likely to be inhibited by generally achievable urine levels. A report of "intemediate" indicates that the test results be considered equivocal or indeterminate. A report of "resistant" indicates that achievable concentrations of the antibiotic are unlikely to be inhibitory and other therapy should be selected.
Certain strains of Enterobacteriaceae exhibit heterogeneity of resistance to cinoxacin. These strains produce isolated colonies within the inhibition zone. When such strains are encountered, the clear inhibition zone should be measured within the isolated colonies.
Standardized procedures require the use of laboratory control organisms. The 100-µg cinoxacin disk should give the following zone diameter:
|Organism||Zone diameter (mm)|
|E.coli ATCC 25922||26-32|
Other quinolone antibacterial disks should not be substituted when performing susceptibility tests for cinoxacin because of spectrum differences between cinoxacin and other quinolones. The 100-µg cinoxacin disk should be used for all in vitro testing of isolates.
Dilution Techniques: Broth and agar dilution methods, such as those recommended by the NCCLS (M7-A3- Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically 1993), may be used to determine the MIC of cinoxacin.Â² MIC test results should be interpreted according to the following criteria (these criteria only apply to isolates from urinary tract infections):
|Zone diameter (mm)||Interpretation|
As with standard diffusion methods, dilution procedures require the use of laboratory control organisms. Standard cinoxacin powder should give the following MIC values:
|Organism||MIC range (µg/mL)|
|E.coli ATCC 25922||2.0-8.0|
Crystalluria, sometimes associated with secondary urinary tract pathology, occurs in laboratory animals treated orally with cinoxacin. In the rhesus monkey crystalluria (without urinary tract pathology) has been noted at doses as low as 50 mg/kg/day (lowest dose tested). Cinoxacin-related crystalluria has not been observed in humans receiving twice the recommended daily dosage.
Some drugs of this class have been shown to have oculotoxic potential. Cinoxacin administered to cats at high dosages (200 mg/kg/day) resulted in retinal degeneration and other ocular changes. The dog appeared to be somewhat resistant to these effects, but high dosages (500 mg/kg/day) resulted in mild retinal atrophy. No cinoxacin-related ocular changes were noted in rabbit, rat, monkey, or human studies. (In one of the studies involving the monkey, cinoxacin was administered for 1 year at 10 times the recommended clinical dose.)
Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.
Additional Cinobac Information
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