-Drug-induced QT interval prolongation is a critical issue in development of new chemical entities, so the pharmaceutical industry needs to evaluate risk as early as possible. Common marmosets have been in the limelight in early-stage development due to their small size, which requires only a small amount of test drug. The purpose of this study was to determine the utility of telemetered common marmosets for predicting drug-induced QT interval prolongation. Telemetry transmitters were implanted in common marmosets (male and female), and QT and RR intervals were measured. The QT interval was corrected for the RR interval by applying Bazett's and Fridericia's correction formulas and individual rate correction. Individual correction showed the least slope for the linear regression of corrected QT (QTc) intervals against RR intervals, indicating that it dissociated changes in heart rate most effectively. With the individual correction method, the QT-prolonging drugs (astemizole, dl-sotalol) showed QTc interval prolongations and the non-QT-prolonging drugs (dl-propranolol, nifedipine) did not show QTc interval prolongations. The plasma concentrations of astemizole and dl-sotalol associated with QTc interval prolongations in common marmosets were similar to those in humans, suggesting that the sensitivity of common marmosets would be appropriate for evaluating risk of drug-induced QT interval prolongation. In conclusion, telemetry studies in common marmosets are useful for predicting clinical QT prolonging potential of drugs in early stage development and require only a small amount of test drug.
Purpose: In acute stroke patients when initiating Nasal-gastric tube feeding (NGF) have a high risk for aspiration pneumonia, which may be related to the body position. We investigated the relationship between body position during NGF and aspiration pneumonia. Method: We enrolled consecutive acute stroke patients, 1) who were admitted from June 2011 to May 2012, 2) with a diagnosis of acute stroke within five days, and 3) who initiated NGF within two days from admission due to altered mental state or severe dysphagia. We allocated these enrolled patients into two Group alternately according to the body position during NGF; patients in the complete lateral position (Group L [n=27]) with keeping nonparalyzed side below and head up at 30-60 degrees during NGF, and patients in the spine position (Group S [n=26]) with head up at 30-60 degrees. We evaluated patients’ baseline characteristics including neurological status and vital signs, inflammatory response parameters, and the number of patients with aspiration pneumonia. Aspiration pneumonia fit three criteria: 1) at least one event of aspiration during NGF, 2) infiltrative shadows on the plain chest radiograph, and 3) no evidence of community acquired pneumonia. Results: We finally evaluated 47 patients (median age was 85 years old, 43% female). There were 32 patients with cerebral infarction and 15 with intracranial hemorrhage, median NIHSS score on admission was 17.5, and on the seventh day was 18 respectively. We analyzed 24 patients in Group L, and 23 in Group S. There was no difference in patients’ baseline characteristics, and inflammatory reaction parameters between the groups statistically significantly. However, the number of patients with aspiration pneumonia after admission was lower in Group L compared to Group S statistically significantly ( nine cases in Group L, 9 cases in Group S, P=0.034). Conclusion: The complete lateral position during the NGF has the potential to prevent aspiration pneumonia for acute stroke patients
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