Double-blind, comparative study of rufloxacin once daily versus amoxicillin three times a day in treatment of outpatients with exacerbations of chronic bronchitis

The efficacy and safety of rufloxacin (400 mg, single dose) were compared to those of norfloxacin (400 mg twice a day for 3 days) for the treatment of women with uncomplicated cystitis. In addition, urine levels, drug level/MIC ratio, and urine antibacterial activity 72 to 84 h after treatment initiation were determined in a subgroup of patients for pharmacodynamic assessment. A total of 203 women were included and treated in this open, randomized clinical trial; 100 patients received norfloxacin, whereas 103 received rufloxacin. Of these, 156 (74 and 82 patients in the norfloxacin and rufloxacin groups, respectively) were considered bacteriologically evaluable. At the first follow-up visits (3 to 12 days after starting the treatment), bacteriological cure rates were 99 and 94% for norfloxacin and rufloxacin, respectively. Seventy-nine percent (119 of 150) of bacteriologically cured patients attended a long-term follow-up visit (4 to 6 weeks after starting the treatment), where a relapse rate of 4% (2 of 54) and 5% (3 of 64) were found in the norfloxacin and rufloxacin groups, respectively. The pharmacodynamic evaluation performed in 35 patients showed similar median urine levels (approximately equal to 25 micrograms/ml) and urine antibacterial activity for both treatment groups against initial isolates, despite a higher norfloxacin level/MIC ratio due to the lower MIC of norfloxacin. Twenty-one patients (20%) in the rufloxacin group and 12 patients (12%) in the norfloxacin group reported 39 and 16 adverse events, respectively, almost all of them being mild and lasting < 24 h. Overall, gastrointestinal reactions were the most frequent adverse events reported. However, 12 patients treated with rufloxacin reported 15 central nervous system adverse events. This study shows that single doses of rufloxacin are as effective as a norfloxacin 3-day standard treatment in uncomplicated cystitis. The results obtained with rufloxacin are consistent with its pharmacodynamic properties.

Section: Discussionsupporting

confidence: 88%

Single-dose rufloxacin versus 3-day norfloxacin treatment of uncomplicated cystitis: clinical evaluation and pharmacodynamic considerations

Rió

Dalet

Aguilar

et al. 1996

“…Steady high concentrations (60 ,ug/ml) of rufloxacin are attained in urine up to 72 h following administration of a single 400-mg dose (37). In view of its pharmacokinetic profile, it can be used once daily for the treatment of urinary (5,24) and respiratory tract (20) infections. It is metabolized at a low level.…”

mentioning

confidence: 99%

In vitro antimycoplasmal activities of rufloxacin and its metabolite MF 922

Furneri

Bisignano

Cerniglia

et al. 1994

Self Cite

The in vitro activities of rufloxacin and its metabolite, MF 922, were compared with those of ofloxacin, ciprofloxacin, erythromycin, and minocycline against Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasmafermentans, and Ureaplasma urealyticum. Rufloxacin, MF 922, and ciprofloxacin shared similar activities against all mycoplasmas tested. (MICs for 90%Yo of isolates tested [MIC90s], 0.5 to 4 ,ig/ml). Ofloxacin had the lowest MIC%0s for U. urealyticum, M. fermentans, and M. hominis (MIC90s, 0.25 to 1 ,ug/ml) and erythromycin had the lowest MIC90 for M. pneumoniae (MIC90, 0.004 ,ug/ml).Fluoroquinolones represent a new class of broad-spectrum antimicrobial agents which are active against gram-negative and many gram-positive organisms. These compounds are bactericidal and generally have good pharmacokinetic and safety profiles. However, some pathogens, including mycoplasmas, are not sufficiently susceptible at low concentrations to many of the quinolones tested (1-3, 7-9, 16-18, 21, 22, 25, 27, 33, 34). Several new compounds have been developed in an attempt to broaden the spectrum of activity, increase the potency, and enhance the disposition of the drug at infection sites. Fig. 1) is a new oral 6-fluoroquinolone with a broad spectrum of activity against gram-negative and grampositive aerobic bacteria and some intracellular pathogens, including Chlamydia pneumoniae and Legionella pneumophila (10,23,36). In vitro, the antibacterial activity of rufloxacin is similar to that of norfloxacin (36), while in animal models it has activity similar to that of ciprofloxacin (12). In humans pharmacokinetic studies have demonstrated that rufloxacin is eliminated slowly, with a half-life in plasma of about 35 h (14,19,37). The drug penetrates well into most body fluids, tissues, and cells, where it reaches high and stable concentrations, ranging from 2 to 25 times those in plasma (4,19,35,37). Particularly high concentrations are achieved in epithelial lining fluid (peak mean values, 42 ,ug/ml) and alveolar macrophages (peak mean values, 88 ,ug/ml) (35). Steady high concentrations (60 ,ug/ml) of rufloxacin are attained in urine up to 72 h following administration of a single 400-mg dose (37). In view of its pharmacokinetic profile, it can be used once daily for the treatment of urinary (5, 24) and respiratory tract (20) infections. It is metabolized at a low level. The N-desmethyl derivative (MF 922) (Fig. 1) is the only microbiologically active metabolite detected. In urine it accounts for 2% of the given dose (19). The in vitro activity of MF 922 is comparable to that of the parent compound (36). However, their effects on mycoplasmas have not been described previously. Rufloxacin (The objective of the study described here was to determine the in vitro susceptibilities of Mycoplasma pneumoniae, Myco- plasma hominis, Mycoplasma fermentans, and Ureaplasma urealyticum to rufloxacin and MF 922 compared with those of ofloxacin, ciprofloxacin, erythromycin, and minocycline. Minocycline was selected rather than tetracycline bec...

“…Available data from clinical trials suggest that rufloxacin, besides its efficacy against other infectious diseases such as urinary tract infections (10,20), is a suitable drug for the treatment of patients with chronic obstructive pulmonary infections (11,23,30). These patients often require theophylline, a bronchodilator, for the treatment of bronchospasms.…”

mentioning

confidence: 99%

Absence of Effect of Rufloxacin on Theophylline Pharmacokinetics in Steady State

Kinzig‐Schippers

Fuhr

Cesana

et al. 1998

Several quinolone antibacterial agents are known to inhibit the metabolism of theophylline, with the potential to cause adverse events due to raised theophylline concentrations during coadministration. A randomized crossover study was therefore conducted with 12 healthy male volunteers (ages, 23 to 34 years; body weight, 64 to 101 kg) to evaluate a possible interaction between rufloxacin and theophylline. Both drugs were administered at steady state. Following the administration of an oral loading dose of 400 mg on day 1, rufloxacin was given orally at 200 mg once daily on days 2 to 7 during one period only. During both periods, 146 mg of theophylline was administered orally twice daily for 3 days (which were days 4 to 6 of the rufloxacin coadministration period) and intravenously once the next morning to test for an interaction. Theophylline and rufloxacin concentrations were measured by reversed-phase high-pressure liquid chromatography, the pharmacokinetics of theophylline at steady state following administration of the last dose were calculated by compartment-model-independent methods. To compare the treatments, analysis of variance-based point estimates and 90% confidence intervals (given in parentheses) were calculated for the mean ratios of the pharmacokinetic parameters from the test (rufloxacin coadministration) over those from the reference (theophylline without rufloxacin) period. These were as follows: maximum concentration at steady state, 1.01 (0.96 to 1.07); area under the concentration-time curve from 0 to 12 h, 0.98 (0.94 to 1.02); half-life, 0.99 (0.95 to 1.03); total clearance at steady state, 1.02 (0.99 to 1.06); and volume of distribution in the elimination phase, 1.01 (0.97 to 1.05). In conclusion, rufloxacin did not affect theophylline pharmacokinetics at steady state. Therefore, therapeutic coadministration of rufloxacin and theophylline is not expected to cause an increased incidence of theophylline-related adverse events.