Moxifloxacin studies

Moxifloxacin, l-cyclopropyl-7-[(lS,65)-2,8-diazabicyclo[4.3.0]nonan-8-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid, is a fourth-generation synthetic fluoroquinolone antibacterial agent. Photostability of moxifloxacin studies after UVA irradiation in solutions and solid phase, with and without participation of Cu(II), Zn(II), Al(III), and Fe(in), were carried out by TLC-densitometric method and LC-MS/MS method [10] (Figure 14.6). 

Because an infection slows the healing of a corneal abrasion, prophylactic antibiotics are often used. Studies on the efficacy of this are mixed. Discontinue the use of contact lenses until the abrasion is healed and the antibiotic course complete. In contact lens wearers, choose an antibiotic that covers Pseudomonas aeruginosa, like gentamicin ointment or solution or a fluoroquinolone.3 Antibiotic resistance is an increasing problem. Resistance occurs primarily with older antibiotics, but has been reported for fluoroquinolones as well. Two newer fluoroquinolones, gatifloxacin and moxifloxacin, do not yet have reports of resistance. These agents are more expensive.6... 

Card/ac e/fecfs Asymptomatic, nonspecific T-wave inversions were observed in 1 study more often in subjects receiving trospium than in subjects receiving moxifloxacin or placebo following 5 days of treatment. This finding was not observed during routine safety monitoring in 2 other placebo-controlled clinical trials in 591 trospium-treated overactive bladder patients. The clinical significance of T-wave inversion in this study is unknown. 

Intravenous conivaptan had no effects on the electrocardiogram in a randomized, single-blind, placebo- and positive-controlled, parallel-group study, in which an intravenous loading dose of conivaptan of 20 mg was followed by a continuous infusion of 40 or 80 mg/day for 4 days or moxifloxacin 400 mg/day for 4 days (9). 

In a pooled analysis of 30 (26 controlled, 4 uncontrolled) prospective, phase II/III studies of oral or intravenous moxifloxacin in 8474 subjects no drug-related hypoglycemic events were reported (732). 

Gavin JR 3rd, Kubin R, Choudhri S, Kubitza D, Himmel H, Gross R, Meyer JM. Moxifloxacin and glucose homeostasis a pooled-analysis of the evidence from clinical and postmarketing studies. Drug Saf 2004 27(9) 671-86. 

U V-resonance Raman spectroscopy is not only used for bacterial identification but also to study the influence of antibiotics on bacterial cells. The mode of action of amikacin on Pseudomonas aeruginosa cells was studied by Lopez-Diez et al. [83], Neugebauer et al. monitored the effect of ciprofloxacin and moxifloxacin on the chemical composition of B. purnilus and Staphylococcus epidermidis [62, 84],... 

A very comprehensive multicenter, randomized, double-blind study of two parallel treatment arms (the MOSAIC study MOxifloxacin compared to Standard therapy in Acute Infectious exacerbations of Chronic infections) demonstrated the powerful clinical activity of moxifloxacin for the treatment of AECB. Five-day treatment with moxifloxacin (400 mg, once daily for 5 days) was found to produce clinical cure rates that were superior to those achieved with 7-day treatment with a standard antibiotic (amoxicillin 500 mg three times daily for 7 days clarithromycin 500 mg twice daily for 7 days cefuroxime 250 mg twice daily for 7 days) [184]. 

In ABS caused by penicillin-resistant S. pneumoniae, moxifloxacin is recommended as the agent of first choice. A study has shown that a cure rate of 97% is obtained with 7-day treatment, and a cure rate of 100% with 10-day treatment [185],... 

The powerful activity of the more recent fluoroquinolones moxifloxacin, gati-floxacin and levofloxacin against clinical isolates of S. pneumoniae, H. influenzae and M. catarrhalis isolated in various European countries in 2000-2001 and the low rates of resistance to these compounds have been demonstrated in a clinical study [190]. 

A comparative study of the pharmacokinetic and pharmacodynamic properties of the more modern fluoroquinolones [218,219], as well as overviews on the pharmacokinetics [163,220] and pharmacodynamics [221] of moxifloxacin, can be found in the literature. 

With regard to drug interactions, it is important to note that the cytochrome P-450 system is not involved in the metabolism of moxifloxacin. In vitro studies using cytochrome P-450 enzymes have shown that moxifloxacin does not inhibit the enzymes CYP 1A2, CYP 3A4, CYP 2C9, CYP 2C19, and CYP 2D6. Moxifloxa-cin s metabolic profile makes it highly unlikely that it will alter the pharmocoki-netics of drugs affected by these enzymes. In rhesus monkeys, oxidative phase I biotransformations do play an additional role, however [272,273]. 

Preservatives have been a differentiating point for the ophthalmic fourth-generation fluoroquinolones. In the United States gatifloxacin ophthalmic solution is preserved with benzalkonium chloride 0.005%, whereas moxifloxacin drops contain no preservative. Although several studies have attributed advantages or disadvantages related to the preservatives (or lack thereof), clinically no differences have been found. 

Preclinical and clinical trial data and data from phase IV studies have shown that levofloxacin, moxifloxacin, and gatifloxacin cause prolongation of the QT interval, but that the potential for torsade de pointes is rare and is influenced by several independent variables (for example concurrent administration of class la and III antidysrhyth-mic agents) (25). There is a moderate increase in the QT interval associated with sparfloxacin, averaging 3%, and the few serious adverse cardiovascular events that have been reported during postmarketing surveillance all occurred in patients with underlying heart disease (26). 

The photosensitizing effect of grepafloxacin is relatively weak and similar to that of ciprofloxacin (38). In one study, one of 207 patients taking grepafloxacin 400 mg/day and six of 204 taking 600 mg/day developed phototoxicity (17). Moxifloxacin is not phototoxic (78). Data obtained in albino mice have suggested that the phototoxic potential of sitafloxacin is milder than that of lomefloxacin or sparfloxacin (79). 

In an in vitro study, ciprofloxacin, grepafloxacin, levo-floxacin, moxifloxacin, ofloxacin, and sparfloxacin had similar good activity against Haemophilus influenzae and Moraxella catarrhalis (112). Against S. pneumoniae (irrespective of the strain s susceptibility to penicillin), grepafloxacin, levofloxacin, moxifloxacin, and sparfloxacin had better activity than ciprofloxacin and ofloxacin. 

In an open, randomized, crossover study, the absolute systemic availability of a single 100 mg dose of moxifloxacin was 0.92 in 10 healthy men (mean age 29 years) (8). There was no evidence of active tubular secretion. Both the oral and intravenous formulations were well tolerated, with five reported possible or probable drug-related adverse events, including headache, nausea, and localized urticaria. 

In a prospective pharmacokinetic study in 12 healthy men the most frequent adverse events, possibly or probably related to moxifloxacin, were generally mild or moderate and were mostly diarrhea, nausea, and abdominal pain (22). 

The effect of food on the pharmacokinetics of moxifloxacin was not clinically important (29). In another study dairy... 

Patel T, Pearl J, Williams J, Haverstock D, Church D. Efficacy and safety of ten day moxifloxacin 400 mg once daily in the treatment of patients with community-acquired pneumonia. Community Acquired Pneumonia Study Group. Respir Med 2000 94(2) 97-105. 

Hoeffken G, Meyer HP, Winter J, Verhoef L CAPl Study Group. The efficacy and safety of two oral moxifloxacin regimens compared to oral clarithromycin in the treatment of community-acquired pneumonia. Respir Med 2001 95(7) 553-64. 

In a randomized, multiple-dose, period-balanced, three-way, crossover study in healthy nonsmoking male volunteers, moxifloxacin did not alter the pharmacokinetics of theophylline (77). 

Quinolones. Levofloxacin, ciprofloxacin, and moxifloxacin are sometimes used to treat MDR-TB. Moxifloxacin also is being studied as a possible replacement for certain first line agents, but data are not available at this time. Quinolones are useful because most are available in oral and intravenous dosage forms, so they can be used in critically ill patients. 

Salisbury VC, Pfoestl A, Weisinger-Mayr H, Lewis R, Bowker K, MacGowan AP. Use of a clinical Escherichia coli isolate expressing lux genes to study the antimicrobial pharmacodynamics of moxifloxacin. J Antimicrob Chemother 1999 43 829-32. 

Ofloxacin and levofloxacin cause moderate increases in the serum levels of procainamide, whereas ciprofloxacin has a lesser effect However, the ECG appears to be unaltered in studies in healthy subjects given these quinolones with procainamide. An increased risk of torsade de pointes would be expected if procainamide is used with gatifloxacin, moxifloxacin, or sparfloxacin, and possibly levofloxacin. 

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