Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040425 (tonsillitis)
 1,594 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Replidyne is developing faropenem medoxomil, the ester-type prodrug of faropenem, for the treatment of bacterial infections and respiratory tract infections, including acute exacerbations of chronic bronchitis (AECB), acute bacterial sinusitis (ABS) and community-acquired pneumonia (CAP). Faropenem medoxomil is also being developed for the treatment of tonsillitis, pharyngitis and otitis media in children. Faronpenem medoxomil was discovered by scientists at Suntory Institute for Biomedical Research (now Asubio Pharma). The compound has significantly improved oral bioavailability and is dehydropeptidase-I stable. Following absorption, faropenem medoxomil is rapidly hydrolysed to the active drug faropenem. An NDA was filed in the US but was deemed not approvable by the US authorities. Following the termination of the license agreement between Replidyne and Forest Laboratories, Replidyne is now exploring other partnering opportunities for faropenem medoxomil. Daiichi Suntory Pharma (now Asubio Pharma) has granted Replidyne the exclusive rights to faropenem medoxomil for the US and Canada and an exclusive option to develop and commercialize the compound in the rest of the world, excluding Japan. Replidyne has rights to the preclinical and clinical data generated up to the time of the agreement (August 2004) and will complete clinical development of the drug. Replidyne is also developing a paediatric formulation for the treatment of common bacterial infections. In February 2006, Replidyne sublicensed development, commercialization and distribution rights of faropenem medoxomil in the US to Forest Laboratories Holdings (Forest Laboratories). However, the agreement was terminated in February 2007, following the US FDA's non-approvable letter for the product. Replidyne re-acquired all US adult and paediatric rights previously granted to Forest. Bayer AG previously licensed exclusive worldwide rights to develop faropenem medoxomil from Suntory (now Asubio Pharma) and conducted a number of phase III clinical trials. This agreement appears to have been superseded by the agreement with Replidyne in 2004. In April 2007, Daiichi Asubio Pharma was renamed as Asubio Pharma Co., Ltd. Daiichi Asubio Pharma was the name used by Daiichi Suntory Pharma after it became a wholly owned subsidiary of Daiichi Pharmaceutical in September 2005. Daiichi Suntory Pharma was the joint venture company owned by Daiichi Pharmaceutical and Suntory. In April 2006, Daiichi Pharmaceutical merged with Sankyo to form Daiichi Sankyo Inc. The FDA issued a non-approvable letter in October 2006 for faropenem medoxomil in the treatment of ABS, CAP, AECB and uncomplicated skin and skin structure infections. Consequently, drug development has reverted back to phase III in the US. The agency has indicated that four phase III trials in three adult respiratory indications, ABS, CAP and AECB, will be required for a US marketing application. According to this advice, Replidyne may be required to conduct one superiority study (versus placebo) each for the ABS and AECB indications and two non-inferiority, active-controlled studies for the treatment of CAP. The required dose of faropenem medoxomil in future trials will be 600 mg, administered twice daily, and trials will involve approximately 1500 patients to ensure an acceptable database of safety information for review. Replidyne is continuing to work with the FDA on further trial details. Replidyne first filed the NDA seeking approval for faropenem medoxomil in December 2005. This submission marked the first marketing approval application for faropenem medoxomil worldwide. The NDA, which was accepted in February 2006, was primarily based on data from 11 phase III trials in patients with respiratory tract and skin infections; the safety data included information from more than 5000 patients treated with the drug. The proposed commercial name for faropenem medoxomil, Orapemtrade mark, was not approved by the FDA due to its similarity to another commercially approved drug. Replidyne and the FDA are working together to identify a suitable alternative. Two phase III trials have been conducted that demonstrated faropenem medoxomil was non-inferio o azithromycin and clarithromycin in the treatment of AECB. Replidyne's phase II trial evaluating an oral liquid formulation of faropenem medoxomil (7.5-40 mg/kg) in paediatric patients with acute otitis media (AOM), met its primary endpoint. The trial was completed in March 2007 and enrolled approximately 310 patients in Costa Rica and Israel. Replidyne intends to meet with the US authorities to discuss the design of the planned phase III trial in paediatric AOM. In addition to 5 years of Hatch-Waxman exclusivity granted upon approval, faropenem medoxomil is protected by an issued US composition of matter patent, which expires in 2015. Extension of exclusivity under Hatch-Waxman legislation is expected.
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PMID:Faropenem medoxomil: A0026, BAY 56-6854, BAY 566854, faropenem daloxate, SUN 208, SUN A0026. 1829 29

Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells have a key role in host defence against infectious pathogens, but their response to bacteria is not well characterized. Non-typeable Haemophilus influenzae is a major cause of respiratory tract infection including otitis media, sinusitis, tonsillitis and chronic bronchitis (especially in chronic obstructive pulmonary disease and bronchiectasis). This bacterium is also present in the pharynx of most healthy adults. The primary factor that may determine whether clinical disease occurs or not is the nature of the lymphocyte response. Here we examined the CTL cell and NK cell responses to nontypeable H. influenzae in healthy control subjects and in subjects who had bronchiectasis and recurrent bronchial infection with this bacterium. Cells were stimulated with live H. influenzae and intracellular cytokine production and release of cytotoxic granules measured. Control subjects had significantly higher levels of interferon gamma production by both CTL and NK cells, while levels of cytotoxic granule release were similar in both groups. The main lymphocyte subsets that proliferated in response to H. influenzae stimulation were the CTL and NK cells. The results suggest that CTL and NK cell responses may be important in preventing disease from nontypeable H. influenzae infection.
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PMID:Cytotoxic T lymphocyte and natural killer cell responses to non-typeable Haemophilus influenzae. 1846 10

Cefuroxime is the first commercially-available second-generation cephalosporine to be widely used in therapy; it is a semi-synthetic cephalosporin obtained from the 7-cephalosporanic acid nucleus of cephalosporin C. Cefuroxime axetil is the acetoxyethyl ester of cefuroxime. The majority of micro-organisms associated with respiratory infections are highly sensitive to cefuroxime. These include Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes and the other streptococci (excluding group D streptococci), and Moraxella catarrhalis. Bacteria sensitive to cefuroxime include the enterobacteria (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Salmonella and Shigella and Straphylococcus aureus (methicillin-sensitive strains). The pharmacokinetic studies show that the maximum plasma concentration of cefuroxime after oral administration of 250 mg and 500 mg of cefuroxime axetil after a meal are respectively 4.6 and 7.9 mg/l. The absolute bioavailability of tablets is 68% (extremes 63-73%) after oral administration of 500 mg cefuroxime axetil. The protein binding is 33+/-5.7%. Tissue diffusion was studied in the interstitial fluid, the bronchial mucosa, the tonsils, and the bronchial secretions. Cefuroxime axetil is available as capsule-shaped tablets containing 125, 250 or 500 mg. An oral suspension dosage form for paediatric purposes is also available as granules in multidose bottles and sachets. Constitution gives a suspension containing 125 mg or 250 mg cefuroxime (as cefuroxime axetil). Cefuroxime axetil is indicated for the treatment of infections caused by susceptible bacteria. Indications include: lower respiratory tract infections (e.g., acute and chronic bronchitis and pneumonia); upper respiratory tract infections (e.g., ear, nose and throat infections such as otitis media, sinusitis tonsillitis and pharyngitis); genito-urinary tract infections (e.g., pyelonephritis, cystitis and urethritis, gonorrhoea, acute uncomplicated gonococcal urethritis and cervicitis); and skin and soft tissue infections (e.g., furunculosis, pyoderma and impetigo). For most infections, a dose of 250 mg twice daily is appropriate. In some urinary tract infections, 125 mg twice daily has been shown to be effective. If pneumonia is suspected or in more severe lower respiratory tract infection, doses of 500 mg bd should be used. Uncomplicated gonorrhoea has been shown to respond to a single 1-g dose of cefuroxime axetil. Adverse reactions to cefuroxime have generally been mild and transient in nature (gastrointestinal disturbances, including diarrhoea, nausea and vomiting).
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PMID:Cefuroxime axetil. 1861 87

Fifteen years after its licensure, this revision assesses the role of cefditoren facing the current pharmacoepidemiology of resistances in respiratory human-adapted pathogens (Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae and Moraxella catarrhalis). In the era of post- pneumococcal conjugate vaccines and in an environment of increasing diffusion of the ftsI gene among H. influenzae isolates, published studies on the cefditoren in vitro microbiological activity, pharmacokinetic/pharmcodynamic (PK/PD) activity and clinical efficacy are reviewed. Based on published data, an overall analysis is performed for PK/PD susceptibility interpretation. Further translation of PK/PD data into clinical/microbiological outcomes obtained in clinical trials carried out in the respiratory indications approved for cefditoren in adults (tonsillitis, sinusitis, acute exacerbation of chronic bronchitis and community-acquired pneumonia) is commented. Finally, the role of cefditoren within the current antibiotic armamentarium for the treatment of community respiratory tract infections in adults is discussed based on the revised information on its intrinsic activity, pharmacodynamic adequacy and clinical/bacteriological efficacy. Cefditoren remains an option to be taken into account when selecting an oral antibiotic for the empirical treatment of respiratory infections in the community caused by human-adapted pathogens, even when considering changes in the pharmacoepidemiology of resistances over the last two decades.
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PMID:Revisiting cefditoren for the treatment of community-acquired infections caused by human-adapted respiratory pathogens in adults. 3041 Jul 57


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