Steady-State Pharmacokinetics of Rufloxacin in Elderly Patients with Lower Respiratory Tract Infections

The present study was designed to determine the effects of an antacid suspension containing magnesium hydroxide and aluminum hydroxide (30 ml of Maalox) on the oral bioavailability of rufloxacin (400 mg). Rufloxacin was administered oraly to 12 healthy volunteers according to a randomized, balanced, crossover design. Three treatments were administered to each subject, with a 10-day washout period between treatments; the treatments included rufloxacin alone, rufloxacin taken 5 min after antacid, and rufloxacin taken 4 h before antacid. Administration of antacid within 5 min before the administration of rufloxacin resulted in a substantial decrease in rufloxacin absorption, with a mean percent relative bioavailability compared with control values of 64% (range, 42 to 77%). Administration of antacid 4 h after the administration of rufloxacin slightly affected the absorption of the quinolone (mean relative bioavailablity, 87%; range, 51 to 110%Y). Antacids that contain magnesium and aluminum salts reduce the absorption of rufloxacin. The extent of this interaction depends on the time that elapses between administration of the two drugs.

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Effects of magnesium-aluminum hydroxide antacid on absorption of rufloxacin

Lazzaroni

Imbimbo

Bargiggia

et al. 1993

“…The antibacterial activity of rufloxacin is generally comparable to those of norfloxacin in vitro (13,22) and ciprofloxacin in in vivo models (7,16). Pharmacokinetic studies with both healthy subjects (9,10,12,23) and patients with lower-respiratory-tract infections (4,17) showed that rufloxacin is eliminated slowly, with a plasma half-life (tl,2) of about 35 h. The drug penetrates well into most tissues (1,21,23), and, because of its long t1,2, it can be administered once daily for treatment of urinary (14) and respiratory (5) tract infections. Clinically significant changes in the disposition of rufloxacin occur only in patients with severe renal (15) or hepatic (20) insufficiency.…”

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confidence: 86%

Biliary excretion of rufloxacin in humans

Privitera

Nicastro

Imbimbo

et al. 1993

Rufloxacin is a new once-daily antibacterial fluoroquinolone with a long half-life. The aim of the present study was to evaluate the plasma and biliary kinetics and biliary and urinary excretion of rufloxacin in patients with extrahepatic cholestasis. Twelve patients with total external percutaneous transhepatic biliary drainage were given a single oral dose of 400 mg of rufloxacin. Plasma, bile, and urine samples and fractions were collected over 72 h after drug administration. Rufloxacin and its major metabolite, the N-desmethyl derivative, were measured by high-performance liquid chromatography. Maximum rufloxacin concentrations in plasma and bile (means + standard deviations) were 4.05 + 1.38 ,ug/ml and 8.24 + 7.16 p,g/ml, respectively, and were reached in 4.2 + 3.0 h and 4.2 + 3.5 h, respectively. The terminal elimination half-life of rufloxacin in plasma was 45.1 ± 13.5 h. Apparent plasma clearance was 31.3 + 10.5 ml/min, while biliary clearance was 0.4 ± 0.2 ml/min and renal clearance was 12.7 ± 6.0 ml/min. In 72 h, 0.9%o + 0.8% of the dose given was recovered in bile and 27.2% ± 12.0%O was recovered in urine. Biliary concentrations exceeded the MICs of most common biliary tract pathogens for at least 24 h after administration. The broad antibacterial spectrum of rufloxacin and its high and prolonged biliary concentrations suggest that this drug may be useful for treatment of biliary tract infections.Rufloxacin is a new oral fluoroquinolone characterized by a broad spectrum of activity against gram-negative and gram-positive aerobic bacteria (3). The antibacterial activity of rufloxacin is generally comparable to those of norfloxacin in vitro (13,22) and ciprofloxacin in in vivo models (7, 16). Pharmacokinetic studies with both healthy subjects (9, 10, 12, 23) and patients with lower-respiratory-tract infections (4, 17) showed that rufloxacin is eliminated slowly, with a plasma half-life (tl,2) of about 35 h. The drug penetrates well into most tissues (1, 21, 23), and, because of its long t1,2, it can be administered once daily for treatment of urinary (14) and respiratory (5) tract infections. Clinically significant changes in the disposition of rufloxacin occur only in patients with severe renal (15) or hepatic (20) insufficiency.Although the importance of the concentration of antibiotics in bile for the treatment of biliary tract infections is still a matter of controversy, it is of interest to assess whether the oral administration of fluoroquinolone derivatives produces sufficient biliary concentrations to sterilize the infected bile (2,8). Similarly, a wide-spectrum antibacterial agent administered orally once a day could provide a valid choice for antibiotic prophylaxis in biliary-surgery and endoscopic procedures. The aim of the present study was to investigate the pharmacokinetics and biliary excretion of rufloxacin in jaundiced patients with continuous complete external bile drainage through percutaneous transhepatic catheters.

“…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). The aim of this study was to investigate the penetration of rufloxacin into the CSF of patients with inflamed or uninflamed meninges.…”

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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 ...