Inter- and intrasubject variabilities in the pharmacokinetics of rufloxacin after single oral administration to healthy volunteers

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In a double-blind, randomized, multicenter study, 463 adult women with symptomatic acute uncomplicated cystitis were treated orally with either a 400-mg single dose of rufloxacin (n ‫؍‬ 226) or an 800-mg single dose of pefloxacin (n ‫؍‬ 237). Escherichia coli (78%) and Proteus mirabilis (7%) were the most common isolates from 350 patients with significant pretreatment bacteriuria (uropathogens, Ն10 5 CFU/ml). In the intention-to-treat analysis of patients with significant pretreatment bacteriuria, 343 patients were assessed for bacteriological outcome and 345 were assessed for clinical outcome. The bacteriological cure rate was 88% in the rufloxacin group and 84% in the pefloxacin group (95% confidence interval [CI] for difference in proportions, ؊4 to 12%), while the clinical resolution rate was 85 and 84%, respectively (95% CI, ؊8 to 9%). The per-protocol analysis demonstrated that among the 264 assessable patients, the bacteriological cure rate obtained with rufloxacin at 4 weeks of follow-up was comparable to that with pefloxacin (91 versus 85%; 95% CI, ؊3 to 15%). Among 295 clinically assessable patients, the clinical resolution rate at 4 weeks of follow-up was 89% in the rufloxacin group and 88% in the pefloxacin group (95% CI, ؊6 to 10%). Potentially drug-related adverse events occurred in 19% of the rufloxacin patients and in 18% of the pefloxacin patients. A single oral dose of 400 mg of rufloxacin is as effective and safe as a single oral dose of 800 mg of pefloxacin for the treatment of acute uncomplicated cystitis in women.Acute uncomplicated lower urinary tract infections (UTIs) are common in women. Symptomatic cystitis is expected to occur in at least 10 to 20% of the female population during their lifetime. These infections generally respond well to a number of antimicrobial agents administered for 3 to 5 days (1,27,34). However, the resistance of uropathogens to conventional antibiotics appears to be increasing nationwide (5,7,33). Given their antibacterial activity against gram-negative rods and staphylococci and the high concentrations attainable in urine, fluoroquinolones have an important role in the 3-day treatment of uncomplicated cystitis in women caused by organisms resistant to older antimicrobial agents (1,29,34,37). Fluoroquinolones are also reserved for empirical treatment when the local prevalence of resistance to first-line agents in common uropathogens is high, such as in southern Europe (1,

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confidence: 99%

Randomized, double-blind comparison of single-dose regimens of rufloxacin and pefloxacin for acute uncomplicated cystitis in women. French Multicenter Urinary Tract Infection-Rufloxacin Group

Jardin

Cesana

1995

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“…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).…”

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confidence: 99%

In vitro antimycoplasmal activities of rufloxacin and its metabolite MF 922

Furneri

Bisignano

Cerniglia

et al. 1994

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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...

“…It is rapidly absorbed by the gastrointestinal tract, with a maximal plasma concentration after 4 h (12) of 3 to 5 mg/liter (12,15) and a plasma half-life of 35 h (12). During multipledose administration, the drug shows an accumulation ratio in plasma ranging from 2.4 to 3.5 (3,15).…”

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confidence: 99%

“…The individual fluoroquinolones differ in their physiochemical properties, pharmacokinetic characteristics, and body fluid penetration abilities (10,14). Their lipophilicity (octanol-buffer partition coefficient ϭ 0.37 at pH 7) (1, 7) and the high apparent volume of distribution of 130 to 150 liters (12,15,26,28) account for their high degree of penetration into CSF. However, analysis of comparative data on CSF transport and disposition of quinolones distinguishes between agents with high (e.g., pefloxacin) and low (e.g., ciprofloxacin) levels of availability to the CSF (11,13,21).…”

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confidence: 99%

Penetration of Rufloxacin into the Cerebrospinal Fluid in Patients with Inflamed and Uninflamed Meninges

Moretti

Pauluzzi

Cesana

2000

Forty-four patients scheduled for lumbar puncture (LP) were recruited to determine the level of penetration of orally administered rufloxacin into cerebrospinal fluid (CSF). The patients were divided into three clinical groups: those with normal CSF (groups A 1d and A 7d ), those with aseptic meningitis (group B), and those with bacterial meningitis (group C). Members of group A 1d received a single 400-mg rufloxacin dose, while group A 7d , B, and C constituents had a multiple-dose regimen (one 400-mg dose, followed by one 200-mg dose daily for 6 days). LP was performed on group A 1d members 5 h after they had received treatment, while for group A 7d it was undertaken 5 h after administration of the last dose. For group B, LP was performed 5 h after the first and the last doses, whereas for group C it was undertaken after the first, fourth, and last doses. Concentrations of rufloxacin in simultaneously collected CSF and plasma samples were determined. Mean CSF/plasma rufloxacin concentration ratios ranged from 0.57 to 0.84, depending on the study group. A higher, but not statistically significant, degree of penetration into CSF was observed in patients with bacterial meningitis than in those with normal CSF or aseptic meningitis. These data indicate that rufloxacin diffuses efficiently into the CSF of patients with either inflamed or uninflamed meninges.Although the introduction of antibiotics made bacterial meningitis curable, the morbidity and mortality associated with this disease remain unacceptably high. In a recent review of 493 episodes of bacterial meningitis in adults, the overall case fatality rate was 25% (6).The penetration of an antibacterial drug into the cerebrospinal fluid (CSF) is an important characteristic in terms of its potential use in central nervous system (CNS) infections. In the presence of inflamed meninges, therapeutic concentrations of many antibiotics can be attained in CSF (2). However, in some persons with brain abscesses, early meningitis, or latestage meningitis, only minor impairments of the blood-CSF barrier occur. Dexamethasone, recommended for use in adjunctive therapy for bacterial meningitis, reduces meningeal inflammation (25) and thereby decreases drug penetration into CSF (2, 23). To ensure successful therapy and to prevent relapses, therapeutic concentrations of any antibiotic proposed for the treatment of CNS infections should be achieved even in the presence of uninflamed meninges.Fluoroquinolones are broad-spectrum antimicrobial agents with in vitro and in vivo bactericidal activity against susceptible organisms (10). The individual fluoroquinolones differ in their physiochemical properties, pharmacokinetic characteristics, and body fluid penetration abilities (10,14). Their lipophilicity (octanol-buffer partition coefficient ϭ 0.37 at pH 7) (1, 7) and the high apparent volume of distribution of 130 to 150 liters (12,15,26,28) account for their high degree of penetration into CSF. However, analysis of comparative data on CSF transport and disposition of quinolones ...