[Evaluation of safety and efficacy of tebipenem pivoxil granules for pediatric in pneumonia, otitis media and sinusitis].

We conducted a postmarketing surveillance of tebipenem pivoxil granules (Orapenem® fine granules 10% for pediatric), an oral carbapenem antibacterial agent, between April 2010 and March 2013 to evaluate the safety and efficacy in patients with pneumonia or otitis media, or sinusitis Of 3,547 patients enrolled, 3,540 from whom survey forms were collected were analyzed. Of these 3,540 patients, there were a total of 3,331 patients included in the safety analysis, 2,844 in the efficacy analysis, 2,769 in the clinical efficacy analysis, and 461 in the bacteriological efficacy analysis. The incidence of adverse drug reactions (ADRs) was 9.97% (332/3,331 patients), and the major ADRs were gastrointestinal disorders including diarrhoea in 317 patients (9.52%). Diarrhoea was reported in 313 patients (316 events), which were not clinically significant and 94.9% (297/313 patients) were recovery and/or remission. The overall clinical efficacy rate was 94.0% (2,604/2,769 patients). The clinical efficacy rate by the type of infection was 95.6% (415/434 patients) for pneumonia, 93.7% (1,389/1,482 patients) for otitis media and 93.6% (659/704 patients) for sinusitis. The eradication rate of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis which are major causative organisms in pediatric infection of pneumonia, otitis media and sinusitis were 94.4% (134/142 strains), 92.2% (130/141 strains) and 97.8% (45/46 strains), respectively. The compliance was good in 83.1% of the patients (2,767/3,331 patients). Overall, Orapenem® fine granules 10% for pediatric showed good safety, efficacy, and compliance. These results indicate that Orapenem® fine granules 10% for pediatric is a useful agent in pediatrics with pneumonia or otitis media, or sinusitis.

Multicenter study of pegylated interferon α-2a monotherapy for hepatitis C virus-infected patients on hemodialysis: REACH study.

Many studies have reported poor vital prognosis in hepatitis C virus (HCV)-infected dialysis patients. The rate of HCV-infected dialysis patients in Japan is as high as 9.8%, and antiviral therapy is believed to be important for improving vital prognosis. We conducted a multicenter study to examine the administration method for pegylated interferon α-2a (PEG-IFNα-2a) monotherapy in HCV-infected dialysis. We studied 56 patients: 14 with low viral loads (HCV RNA < 5.0 log IU/mL) were treated with 90 µg PEG-IFNα-2a weekly, 42 with high viral loads (HCV RNA ≥ 5.0 log IU/mL) were treated with 135 µg PEG-IFNα-2a weekly. We examined the sustained virological response (SVR), factors affecting the SVR, and treatment safety. The overall SVR rate was 39% (22/56); that for genotype 1, genotype 2, low viral loads, and high viral loads was 29%, 67%, 93%, and 21%, respectively. From receiver operating characteristic (ROC) analysis, the HCV RNA cutoff values likely to achieve SVR for genotypes 1 and 2 were <5.7 log IU/mL (SVR rate: 64% 9/14) and <6.5 log IU/mL (SVR rate: 88% 7/8), respectively. If there was HCV RNA negativation at 4 weeks (rapid virological response), the SVR rate was 94% (16/17), whereas it was 6% (1/16) if there was HCV RNA positivity at 24 weeks. The rate of treatment discontinuation from adverse events or aggravated complications was 25% (14/56). High SVR rates can potentially be achieved with PEG-IFN monotherapy by identifying the target patients, based on virus type and viral load before initiating treatment and by modifying therapy during treatment according to responsiveness.

Effect of chitosan chewing gum on reducing serum phosphorus in hemodialysis patients: a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: HS219 (40 mg chitosan-loaded chewing gum) is designed to bind salivary phosphorus as an add-on to available phosphorus binders. We performed a randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of HS219 in hemodialysis (HD) patients with hyperphosphatemia as an add-on to phosphorus binders. METHODS: Sixty-eight HD patients who were maintained on calcium carbonate (n=33) or sevelamer hydrochloride (n=35) were enrolled. The primary end point was a change in serum phosphorus levels. Secondary end points included changes in levels of salivary phosphorus, serum calcium, parathyroid hormone (PTH), and intact fibroblast growth factor (iFGF) 23. RESULTS: Sixty-three patients chewed either HS219 (n=35) or placebo (n=28) for 30 min, three times a day, for 3 weeks. HS219 was well tolerated and safe. However, HS219 was not superior to placebo with additional reduction of serum phosphorus with respect to phosphorus binders at the end of the chewing period. There were no significant effects of HS219 on reduction of salivary phosphorus, serum calcium, iPTH, or iFGF23 levels. CONCLUSIONS: The chitosan-loaded chewing gum HS219 does not affect serum and salivary phosphorus levels in Japanese HD patients with hyperphosphatemia. Our findings do not support previous findings that 20 mg of chitosan-loaded chewing gum reduces serum and salivary phosphorus levels. TRIAL REGISTRATION: [corrected] ClinicalTrials.gov NCT01039428, 24 December, 2009.

Observation of beat oscillation generation by coupled waves associated with parametric decay during radio frequency wave heating of a spherical tokamak plasma.

We present an observation of beat oscillation generation by coupled modes associated with parametric decay instability (PDI) during radio frequency (rf) wave heating experiments on the Tokyo Spherical Tokamak-2. Nearly identical PDI spectra, which are characterized by the coexistence of the rf pump wave, the lower-sideband wave, and the low-frequency oscillation in the ion-cyclotron range of frequency, are observed at various locations in the edge plasma. A bispectral power analysis was used to experimentally discriminate beat oscillation from the resonant mode for the first time. The pump and lower-sideband waves have resonant mode components, while the low-frequency oscillation is exclusively excited by nonlinear coupling of the pump and lower-sideband waves. Newly discovered nonlocal transport channels in spectral space and in real space via PDI are described.

[Tissue and aural discharge distribution of tebipenem pivoxil].

Tebipenem pivoxil (TBPM-PI) is a novel oral carbapenem antibiotic. It has been developed as a prodrug of tebipenem (TBPM), to increase absorption. We assessed the distribution of TBPM to aural discharge and tissues after administration of TBPM-PI to adult patients who underwent otolaryngological surgical tissue resection and pediatric patients with acute otitis media or acute sinusitis. Following the administration of single oral doses of 150 and 250 mg (potency) of TBPM-PI to adult patients who underwent otolaryngological surgical tissue resection, tissue TBPM concentrations for the respective doses were 0.38 to 1.76 microg/g and 0.17 to 0.91 microg/g in mucous membranes of the maxillary sinus, 0.26 to 0.94 microg/g and 0.14 to 0.45 microg/g in mucous membranes of the ethmoid sinus, and 0.12 to 0.13 microg/g and 0.14 to 0.47 microg/g in palatine tonsil tissues, as well as 0.29 microg/g in mucous membranes of the middle ear for the dose of 250 mg. The percentages of these tissue concentrations to plasma concentrations for the respective doses were 14.3% to 61.0% and 18.4% to 54.6% in mucous membranes of the maxillary sinus, 34.3% to 52.1% and 9.9% to 54.6% in mucous membranes of the ethmoid sinus, and 10.3% to 15.0% and 6.5% to 17.4% in palatine tonsil tissues, as well as 16.8% in mucous membranes of the middle ear for the dose of 250 mg. Following the administration of TBPM-PI at doses of 4 mg (potency)/kg and 6 mg (potency)/kg twice daily to pediatric patients with acute otitis media or acute sinusitis, TBPM concentrations in the aural discharge for these doses were 0.03 to 2.00 microg/g and 1.07 or 1.18 microg/g, respectively. The percentage of aural discharge concentrations to plasma concentrations for these doses was 0.3% to 86.1% and 40.5% or 83.6%, respectively. These results indicate a favorable distribution profile of TBPM to tissues affected by otitis media or sinusitis after the administration of TBPM-PI and can support the high efficacy of TBPM-PI.