Determination of norfloxacin, a new nalidixic acid analog, in human serum and urine by high-performance liquid chromatography

111

Ciprofloxacin was given orally to 10 healthy volunteers for seven consecutive doses of 250 mg every 12 h. Serum and urine samples were collected at distinct times between 0 and 96 h and analyzed both by high-pressure liquid chromatography and by a microbiological assay. The detection limits were 0.006 and 0.03 ,ug/ml, respectively. For each method, imprecision coefficients of variation were <6.1% at various concentrations in serum and urine. The means + standard deviations of the absolute values of the relative differences between the two methods were 9.3 ± 6.8% (n = 225) for serum samples and 58.5 ± 50.4% (n = 70) for urine samples. Comparison of the concentrations in serum measured with high-pressure liquid chromatography and bioassay by regression analysis yielded a slope which was not significantly different from 1.0 (99.9% confidence limits: 0.984 < slope < 1.035). In urine, however, the bioassay results were markedly higher than the high-pressure liquid chromatography values (1.327 < slope < 1.698), which indicates the presence of antimicrobially active metabolites. The cumulative 12-h urinary recovery after the first and seventh doses averaged 30.2 ± 8.5 and 26.4 ± 4.6%, respectively, by high-pressure liquid chromatography, whereas with bioassay 38.2 ± 5.9 and 45.5 + 5.9% activity was recovered. Protein binding appeared to be neither concentration nor pH dependent and averaged 21.9 ± 4.1%.

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confidence: 97%

“…They required time-consuming extraction and concentration steps for sample preparation, yet the limit of detection was 0.1 ,ug/ml with UV monitoring (2,4). Another method that involved the use of fluorescence detection (after acetylation of norfloxacin) was even less sensitive (11).…”

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confidence: 99%

Comparison of high-pressure liquid chromatography and bioassay for determination of ciprofloxacin in serum and urine

Joos¹,

Ledergerber²,

Flepp³

et al. 1985

111

“…The peak serum and inflammatory tissue levels of norfloxacin and ciprofloxacin are much in excess of the observed MICs of the compounds for N. gonorrhoeae (2,5). Rosoxa-cin has been shown to be effective for the treatment of gonorrhea, due to both penicillinase-negative strains and PPNGs (1,4,7,8).…”

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confidence: 99%

In vitro activities of the spectinomycin analog U-63366 and four quinolone derivatives against Neisseria gonorrhoeae

Peeters¹,

Dyck²,

Piot³

1984

The in vitro activities of the new spectinomycin analog U-63366 and four new quinolone derivatives, rosoxacin, norfloxacin, ofloxacin, and ciprofloxacin, were compared with those of penicillin, tetracycline, thiamphenicol, cefotaxime, ceftriaxone, and spectinomycin against 222 beta-lactamase-negative and 25 betalactamase-positive Neisseria gonorrhoeae strains. U-63366 was more active than spectinomycin, inhibiting 90% of the strains at a concentration of 2 mg/liter. Among the quinolone derivatives, ciprofloxacin was the most active compound in vitro (90% MIC, 0.002 mg/liter), followed by ofloxacin (90% MIC, 0.008 mg/liter), norfloxacin (90% MIC, 0.015 mg/liter), and rosoxacin (90% MIC, 0.03 mg/liter).The emergence of penicillinase-producing isolates of Neisseria gonorrhoeae (PPNGs) and the high MIC of tetracycline among these strains have stimulated the search for alternative antimicrobial agents that are effective against infections with PPNGs as well as with gonococcal strains with reduced susceptibility to penicillin. Spectinomycin has been widely used for the treatment of PPNG infections, and spectinomycin-resistant PPNG strains are still rare (1). Until now, mainly second-and third-generation cephalosporins have been actively investigated as alternative drugs for PPNG infections, and they already are widely used in some countries. However, cefuroxime-resistant N. gonorrhoeae strains have been reported in the Netherlands (6), and isolates resistant to the newer cephalosporins may rapidly emerge (11).We report here on the activity of U-63366, a new spectinomycin analog, and four new quinolone derivatives against penicillinase-negative N. gonorrhoeae isolates and PPNGs.The These results agree with recently published in vitro susceptibilities (7,9,12).Although the MIC50 and MIC90 of the quinolones for the PPNGs were one to three dilutions higher than those for the penicillinase-negative isolates, the overall range of MICs of the four compounds was almost identical for both groups of strains. The slightly higher MICs for the PPNGs may be due to an overall lower susceptibility of these isolates, which were all acquired outside Belgium. PPNGs also exhibited slightly higher median MICs of ceftriaxone and U-63366 but not of cefotaxime and spectinomycin. In contrast, tetracycline and thiamphenicol were much less active against PPNGs, with an eightfold increase in the median MIC of both antibiotics. Thus, more than 50% of the PPNGs had MICs of tetracycline and thiamphenicol of .2 mg and .1 mg, respectively, per liter.The in vitro results suggest that the newer quinolones may be effective drugs for the treatment of gonococcal infection. The peak serum and inflammatory tissue levels of norfloxacin and ciprofloxacin are much in excess of the observed MICs of the compounds for N. gonorrhoeae (2,5). Rosoxa-cin has been shown to be effective for the treatment of gonorrhea, due to both penicillinase-negative strains and PPNGs (1,4,7,8). However, central nervous system side effects of a 200-mg single dose were found in up to ...

“…Its increased potency and expanded antibacterial spectrum compare with those of nalidixic acid (9,13,20,22,23), and its desirable pharmacokinetic properties (4) The anaerobic bacterium Clostridium difficile was less susceptible to norfloxacin (MIC90, 128 ,ug/ml) and to nalidixic acid (MIC90, >128 ,ug/ml) than to other agents and was most susceptible to vancomycin (MIC90, 0.5 ,ug/ml). The MIC9os of norfloxacin against all the aerobic isolates tested were less than 1 ,ug/ml, ranging from 0.008 ,ug/ml for E. coli to 0.5 ,ug/ml for Campylobacter fetus subsp.…”

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confidence: 99%

In vitro antibacterial activity of norfloxacin (MK-0366, AM-715) and other agents against gastrointestinal tract pathogens

Shungu¹,

Weinberg²,

Gadebusch³

1983

A comparison was made of the in vitro activities of norfloxacin and of nine other orally administered antibacterial agents against 180 clinical isolates representing the bacterial species most frequently implicated in infections of the gastrointestinal tract in humans. The 90% minimal inhibitory concentrations showed norfloxacin to be 4, 15, 4, 17, 17, 17, and 33 times more active than the next best compound tested against Campylobacter fetus subsp. jejuni, Escherichia coli, Salmonella spp., Shigella spp., Vibrio cholerae, Vibrio parahaemolyticus, and Yersinia enterocolitica, respectively, with an overall 90% minimal inhibitory concentration of less than or equal to 0.5 micrograms/ml. Norfloxacin was least active against Clostridium difficile (90% minimal inhibitory concentration, 128 micrograms/ml). These results should encourage further evaluation of norfloxacin as a potential chemotherapeutic agent in the treatment of enteric bacterial infections for which antibiotic therapy is indicated.