Disease relevance of loracarbef

• Loracarbef is a new oral antimicrobial of the carbacephem class with in vitro activity against the common pathogens associated with skin infections, otitis media, sinusitis, bronchopulmonary infections, and urinary tract infections [1].
• Results of these studies indicated that loracarbef, 400 and 200 mg twice daily, had clinical and bacteriologic efficacy against the common respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella (Branhamella) catarrhalis that was comparable with that of the comparative agents [2].
• These results suggest that 400 mg loracarbef twice daily for 7 days is effective and safe in the treatment of acute exacerbations of chronic bronchitis [3].
• Thus, these clinical trials support the conclusion that loracarbef is a safe and effective treatment for bacterial pneumonia [4].
• Similarly favorable results were seen when a 7-day regimen of loracarbef (200 mg once a day) was compared with a 7-day regimen of norfloxacin (400 mg twice a day) in a large European study of approximately 300 patients with uncomplicated cystitis [5].

Psychiatry related information on loracarbef

• However, loracarbef can be administered twice daily, offering the advantage of improved patient compliance [6].

High impact information on loracarbef

• In one study conducted in the United States, a 7-day course of once-daily doses of loracarbef (200 mg) was compared with a 7-day course of multiple daily doses of cefaclor (250 mg three times a day) [5].
• Two controlled clinical trials compared loracarbef (LY163892 with amoxicillin/clavulanate or amoxicillin in the treatment of acute exacerbations of chronic bronchitis [3].
• The safety profile of loracarbef: clinical trials in respiratory, skin, and urinary tract infections [7].
• Loracarbef achieves middle-ear and interstitial-fluid levels that generally exceed the minimum inhibitory concentrations for common bacterial pathogens [8].
• Loracarbef (LY163892) in the treatment of acute exacerbations of chronic bronchitis: results of U.S. and European comparative clinical trials [3].

Chemical compound and disease context of loracarbef

• We examined the bactericidal activities of penicillin, cefprozil, cefixime, cefaclor, and loracarbef against three clinical isolates of Streptococcus pneumoniae which were susceptible, moderately susceptible, and resistant to penicillin [9].
• One hundred five infants and children with acute otitis media were randomized to therapy with loracarbef, an experimental carbacephem antibiotic, or amoxicillin-clavulanate (Augmentin), an approved drug for this disease [10].
• We compared the in-vitro activities of cefprozil, a novel oral cephalosporin, and of loracarbef, a new oral carbacephem, with other agents against middle ear fluid isolates obtained from children with acute otitis media [11].
• Sterile culture filtrates from non-typable Haemophilus influenzae (NTHi) grown in medium containing no antibiotics or 0.25 MIC of amoxycillin, ciprofloxacin or loracarbef were examined for their effect on the ciliary beat frequency (CBF) and structure of human respiratory epithelium [12].
• Treatment was discontinued in one loracarbef-treated patient because Ludwig's angina, unrelated to the study drug, was diagnosed and in five amoxicillin/clavulanate-treated patients because of diarrhea (two patients), rash (two patients), and nausea and vomiting (one patient) [13].

Biological context of loracarbef

• Loracarbef, the first beta-lactam antibiotic of the carbacephem class to undergo clinical evaluation, has been the subject of extensive clinical pharmacology studies [8].
• Effects of renal dysfunction on the pharmacokinetics of loracarbef [14].
• Comparison of the acyl-enzyme structures of ceftazidime and loracarbef, a beta-lactam substrate, reveals that the conformation of ceftazidime in the active site differs from that of substrates [15].
• Loracarbef treatment and antiserum enhanced phagocytosis and killing of E. coli and H. influenzae type b to a greater extent than either antibiotic treatment or antiserum alone [16].
• Comparative bioavailability of loracarbef chewable tablet vs. oral suspension in children [17].

Anatomical context of loracarbef

• Loracarbef, a member of the carbacephem class of beta-lactam antibiotics, was tested in randomized, double-blind, parallel studies for the treatment of uncomplicated urinary tract infections (UTIs) [5].
• Peripheral blood mononuclear cells were isolated from each patient and were exposed to cefaclor, loracarbef, and the metabolites of each generated with phenobarbital-induced murine hepatic microsomes [18].
• Both cephalexin and loracarbef are transported by this mechanism into the human intestinal Caco-2 cell line [19].
• On days 7 and 14 of therapy, sputum loracarbef concentrations were similar 4 h after the morning dose (0.23 mg/L following 200 mg; 0.35 mg/L after 400 mg) [20].
• 1. The stereoselective transport of beta-lactam antibiotics has been investigated in the human intestinal epithelial cell line, Caco-2, by use of D- and L-enantiomers of cephalexin and loracarbef as substrates [21].

Associations of loracarbef with other chemical compounds

• Cefprozil and loracarbef activities were unaffected at pH 6 and 8 or in the presence of human serum, but there was a major diminution of activity for both agents at pH 5 and at inoculum sizes greater than or equal to 10(7) cfu/ml [11].
• Influence of subinhibitory concentrations of loracarbef (LY 163892) and daptomycin (LY 146032) on bacterial phagocytosis, killing and serum sensitivity [16].
• In this single-blind study, 488 patients with acute bronchitis were randomly assigned to receive 400 mg of loracarbef twice daily or 500/125 mg of amoxicillin/clavulanate three times daily for seven days [22].
• At any given pH, loracarbef is more stable in solution than any other therapeutically useful cephalosporin [23].
• A double blind, randomized clinical trial compared loracarbef (LY163892) with penicillin VK [24].

Gene context of loracarbef

• Loracarbef (LY163892), a member of the class of beta-lactam antibiotics known as carbacephems, is characterized by a high level of chemical stability and a broad spectrum of antibacterial activity that persists in the presence of beta-lactamase [25].
• Data analyzed from subjects with various degrees of renal dysfunction who were given single oral doses of loracarbef indicated a linear relationship between creatinine clearance (CLCR) and plasma clearance [CLP (L/hr) = 0.106.CLCR (ml/min/1.73 m2)] [14].
• Pre-exposure to loracarbef resulted in increased susceptibility of E. coli and H. influenzae type b to the bactericidal activity of antiserum, but exposure to loracarbef or daptomycin did not modify serum sensitivity of S. aureus [16].
• Mechanism and kinetics of transcellular transport of a new beta-lactam antibiotic loracarbef across an intestinal epithelial membrane model system (Caco-2) [26].
• In vitro activity of loracarbef against TEM extended-spectrum beta-lactamase-producing Escherichia coli strains and its interaction with the enzymes [27].

Analytical, diagnostic and therapeutic context of loracarbef

• The efficacy and safety of the antibiotic loracarbef have been demonstrated in a series of 22 clinical trials involving over 9,000 patients [7].
• Loracarbef possesses a pharmacokinetic profile consistent with the efficacy and safety profile documented in controlled clinical trials [8].
• Two double-blind, randomized clinical trials of loracarbef (LY163892) were conducted [28].
• Loracarbef is readily cleared from plasma by hemodialysis; dosing should be repeated after a hemodialysis treatment [14].
• Ten to sixteen days after treatment, 68.1% of the loracarbef group, compared with 76.1% of the amoxicillin-clavulanate group, showed favorable responses [29].

References