Pharmacokinetics and tissue penetration of rufloxacin, a long acting quinolone antimicrobial agent

Bacterial keratitis is a serious infectious ocular disease requiring prompt treatment to prevent frequent and severe visual disabilities. Standard treatment of bacterial keratitis includes topical administration of concentrated antibiotic solutions repeated at frequent intervals in order to reach sufficiently high drug levels in the corneal tissue to inhibit bacterial growth. However, this regimen has been associated with toxicity to the corneal epithelium and requires patient hospitalization. In the present study, a mucoadhesive polymer extracted from tamarind seeds was used for ocular delivery of 0.3% rufloxacin in the treatment of experimental Pseudomonas aeruginosa and Staphylococcus aureus keratitis in rabbits. The polysaccharide significantly increased the intra-aqueous penetration of rufloxacin in both infected and uninfected eyes. Rufloxacin delivered by the polysaccharide reduced P. aeruginosa and S. aureus in the cornea at a higher rate than that obtained by rufloxacin alone. In particular, use of the polysaccharide allowed a substantial reduction of S. aureus in the cornea to be achieved even when the time interval between drug administrations was extended. These results suggest that the tamarind seed polysaccharide prolongs the precorneal residence times of antibiotics and enhances drug accumulation in the cornea, probably by reducing the washout of topically administered drugs. The tamarind seed polysaccharide appears to be a promising candidate as a vehicle for the topical treatment of bacterial keratitis.

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confidence: 99%

A Mucoadhesive Polymer Extracted from Tamarind Seed Improves the Intraocular Penetration and Efficacy of Rufloxacin in Topical Treatment of Experimental Bacterial Keratitis

Ghelardi

Tavanti

Davini

et al. 2004

“…(15). It has excellent serum and urine concentrations and a particularly long half-life (35 h) with a slow renal elimination, allowing for once-a-day administration (11,16,39). The plasma and urine half-lives of rufloxacin are two times longer than those of pefloxacin (4,23).…”

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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

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,

“…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

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...