Disease relevance of Ritipenem

• Interaction of FCE 22101 with penicillin-binding proteins of Staphylococcus aureus [1].
• The susceptibility of known, characterized beta-lactamase-producing strains of the Enterobacteriaceae suggested that FCE 22101 is resistant to many beta-lactamases [2].
• Pseudomonas aeruginosa strains were resistant to FCE 22101 (minimum inhibitory concentration, greater than 128 micrograms/ml) [2].
• Ritipenem is highly bacteriolytic against Haemophilus influenzae [3].
• Ninety percent of the Neisseria gonorrhoeae and Streptococcus pneumoniae strains were susceptible to 0.25 microgram of FCE 22101 per ml [2].

High impact information on Ritipenem

• Pseudomonas aeruginosa exhibits high intrinsic resistance to penem antibiotics such as faropenem, ritipenem, AMA3176, sulopenem, Sch29482, and Sch34343 [4].
• Microscopic examinations revealed that selective PBP 3 inhibitors, such as aztreonam and cefotaxime, inhibited lysis induced by ritipenem [3].
• FCE 22891 is a prodrug of the penem antibiotic FCE 22101 and is suitable for oral administration [5].
• The in vitro activity of L-627, a new parenterally administered carbapenem, was compared with those of imipenem, meropenem, FCE 22101 (a penem), ceftazidime, and ceftriaxone [6].
• The results of the present study support suggestions that presystemic metabolism of FCE 22101 and/or transformation of the prodrug to compounds other than FCE 22101 are the main cause of intersubject variability in the kinetics of FCE 22101 produced in plasma following oral administration of its prodrug [5].

Chemical compound and disease context of Ritipenem

• Reexamination of Serratia marcescens isolates obtained in 1982 revealed two organisms that were resistant to the penem FCE 22101 (MIC, 512 micrograms/ml) and imipenem (MIC, 16 micrograms/ml) and that had slightly reduced susceptibilities to meropenem (MIC, 0.12 micrograms/ml) [7].
• The combination of FCE 22101 and gentamicin against Streptococcus faecalis was usually additive [8].
• Combinations of FCE 22101 with ciprofloxacin or gentamicin against methicillin-resistant Staphylococcus aureus and methicillin-resistant Staph. epidermidis resulted in addition or indifference by the chequerboard method [8].
• Although FCE 22101 is generally less active against Enterobacteriaceae than are cefotaxime and ceftazidime, it does inhibit some Enterobacter spp. resistant to these agents [9].

Biological context of Ritipenem

• Intersubject variability in the kinetics of total radioactivity in plasma was far less than that observed for FCE 22101 [5].
• The human serum protein binding of FCE 22101 was about 40%, and human serum had little effect on the activity [2].
• Plasma pharmacokinetics of ritipenem and metabolites were time-independent [10].
• Significant levels of the metabolite P1 were observed in blood with peak levels of 1.7 mg/L seen 130 min after dosing, 50 min later than the peak FCE 22101 levels, and giving a mean AUC of 297 mg.min/L [11].
• Rapid hydrolysis in vivo in man of FCE 22891, the orally absorbed ester of FCE 22101 [12].

Anatomical context of Ritipenem

• The average amount of FCE 22101 excreted in urine and feces corresponded to 9.0 and 1.6% of the dose, respectively [5].
• When the classical competitive procedure was modified by increasing the time of incubation of either membranes or growing cells with FCE 22101, the antibiotic showed a much higher affinity for penicillin-binding protein 2a and saturated the protein at a concentration close to the MIC, with slow kinetics [1].
• Dose finding study on the efficacy and safety of ritipenem in complicated urinary tract infections [13].

Associations of Ritipenem with other chemical compounds

• In-vitro activity of two new carbapenems FCE 22101 and CGP 31608 in comparison with imipenem [14].
• This experimental model was used to compare the efficacies of FCE 22101, imipenem, and gentamicin combined with metronidazole in the treatment of intra-abdominal infections [15].
• The most efficient routes for the synthesis of FCE 22101, a penem antibiotic characterized by a carbamoyloxymethyl sidechain at C-2 identical to that of cefuroxime and cefotaxime, and of FCE 22891, its orally absorbed pro-drug, are described [16].
• For comparative purposes, the kinetics of imipenem and cilastatin, given alone or together with FCE 22101, were calculated [17].
• Against Staph. aureus ampicillin was slightly more active than cefuroxime, which showed equivalent activity to FCE 22101, while against Esch. coli and Ent. cloacae cefuroxime and ampicillin were less active than FCE 22101 [18].

Gene context of Ritipenem

• FCE 22891 is the oral prodrug of FCE 22101, a new broad-spectrum penem [19].
• The activity of the antibiotics against beta-lactamase-producing strains was also tested and here FCE 22101 exhibited the greatest inhibitory effect on bacterial growth [18].
• The pneumococcal strains included lyt- mutants in which the autolysin gene was inactivated or deleted and clinical isolates with penicillin MIC greater than 1.0 mg/l. The killing activity of FCE 22101 was superior to that of penicillin for all strains [20].
• High-performance liquid chromatographic methods for the determination of the penems SCH 29482 and FCE 22101 in human serum and urine [21].
• Chromatographic separation of FCE 22101 was achieved using an SP8700 solvent delivery system (Spectra-Physics), an SP8780XR autosampler (Spectra-Physics) and a reverse-phase C18 mu-BondaPak column (8 X 100 mm) radially compressed in a Z module (Millipore, UK) [22].

Analytical, diagnostic and therapeutic context of Ritipenem

• Urine samples obtained at timed intervals were assayed for FCE 22101 and its metabolites P1 and P2 by HPLC [23].
• Plasma and urine concentrations of FCE 22101, and in the cross-over study also its open ring metabolites P1 and P2, were determined by HPLC [24].
• The 24 h urinary recoveries of the parent drug and its metabolites were similar after treatments A and B. Mean recoveries +/- S.D were 29 +/- 13% (FCE 22101), 31 +/- 12% (P1) and 7 +/- 2% (P2) of the dose [23].
• The urinary recovery and tolerability of FCE 22101, a broad spectrum injectable penem, were investigated in a multicentre single-blind randomized crossover study of 60 healthy male volunteers [23].
• A high performance liquid chromatography method for the determination of FCE 22101, a novel penem antimicrobial, in serum [22].

References